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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 5  |  Issue : 1  |  Page : 60-67

Selenium as a therapeutic adjuvant for isoniazid/rifampicin-induced hepatotoxicity


Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Bayelsa State, Nigeria

Date of Submission21-Dec-2019
Date of Decision18-Feb-2020
Date of Acceptance24-Feb-2020
Date of Web Publication08-Jul-2020

Correspondence Address:
Dr. Elias Adikwu
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Bayelsa State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bjhs.bjhs_65_19

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  Abstract 


BACKGROUND: Isoniazid-rifampicin (INH-RIF) is used for the treatment of tuberculosis, but its hepatotoxicity is a serious health predicament. Selenium (Se) is a trace element with potential to safeguard cells from damage.
AIM AND OBJECTIVE: This study assessed the potential of Se to prevent INH/RIF-induced hepatotoxicity in albino rats.
MATERIALS AND METHODS: Forty-five adult male albino rats were randomly assigned to four groups. Group 1A (Placebo control) and Group 1B (Solvent control) were orally treated with normal saline (0.2mL) and corn oil (0.2mL) daily for 21 days, respectively. Group 2 (2A–2C) was orally treated with Se (0.1, 0.2, and 0.4 mg/kg) daily for 21 days. Group 3 was orally treated with INH-RIF (50/100 mg/kg) daily for 21 days. Group 4 (4A–4C) was orally pretreated with Se (0.1, 0.2, and 0.4 mg/kg) before oral treatment with INH-RIF (50/100 mg/kg) daily for 21 days, respectively. After treatment, the rats were weighed and anesthetized. Blood samples were collected and analyzed for serum liver function markers. Liver samples were weighed and analyzed for histology and biochemical indices.
RESULTS: INH-RIF caused significant (P < 0.001) decreases in body weight, superoxide dismutase, glutathione, catalase, and glutathione peroxidase levels with significant (P < 0.001) increases in liver weight, malondialdehyde, alkaline phosphatase, aminotransferases, lactate dehydrogenase, gamma-glutamyl transferase, total bilirubin, and conjugated bilirubin levels, when compared to control. INH-RIF caused liver ischemic necrosis and vascular congestion. Hepatotoxicity induced by INH-RIF was abrogated in a dose-dependent fashion by pretreatment with Se 0.1 mg/kg (P < 0.05), 0.2 mg/kg (P < 0.01), and 0.4 mg/kg (P < 0.001) when compared to INH-RIF.
CONCLUSION: Se may serve as an adjuvant treatment for hepatotoxicity caused by INH-RIF.

Keywords: Isoniazid, liver, rat, rifampicin, selenium, toxicity


How to cite this article:
Adikwu E, Nelson EC, Fiyebo P. Selenium as a therapeutic adjuvant for isoniazid/rifampicin-induced hepatotoxicity. BLDE Univ J Health Sci 2020;5:60-7

How to cite this URL:
Adikwu E, Nelson EC, Fiyebo P. Selenium as a therapeutic adjuvant for isoniazid/rifampicin-induced hepatotoxicity. BLDE Univ J Health Sci [serial online] 2020 [cited 2020 Aug 15];5:60-7. Available from: http://www.bldeujournalhs.in/text.asp?2020/5/1/60/289203



Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that affects people globally. It primarily affects the lungs (pulmonary TB), but can disseminate to other areas of the body (extrapulmonary TB).[1] TB is a serious worldwide health predicament which incidence can be correlated with increasing incidence of acquired immune deficiency syndrome. It is one of the known primary and leading causes of adult death globally, especially in tropical regions.[2] Epidemiological findings showed that over 95% of the incidence of fatal cases of TB recorded in 2015 occurred in low- and middle-income countries.[3]

Isoniazid-rifampicin (INH-RIF) is an essential component offirst-line anti-TB regimen currently used. INH exerts its anti-mycobacterial activity by inhibiting mycolic acid synthesis, which is required for mycobacterial cell wall. The bactericidal activity of RIF involves the inhibition of β-subunit of RNA polymerase present in Mycobacterium tuberculosis.[4] INH-RIF has been very efficient and effect in the fight against TB, but it has been associated with hepatotoxicity ranging from elevations in serum aminotransferases to fulminant liver failure.[5] The hepatotoxic effect of INH-RIF is a serious public health problem due to increase in the prevalence rate with 11.6% reported in India and 4.3% reported in western countries.[6] The hepatotoxic effect of INH-RIF has been associated with INH through the oxidative activation of its biotransformed metabolites in the liver by cytochrome P450 monooxygenase. This generates electrophilic intermediates and free radicals that can cause damage to hepatic tissues through oxidative stress.[7] Furthermore, RIF can potentiate hepatotoxicity caused by INH through oxidative stress and the functional incapacitation of hepatic antioxidants.[8]

Selenium (Se) is an essential micronutrient of major health importance. Naturally, it is incorporated as selenocysteine at the bioactive sites of a number of proteins for biological activities. Under physiological conditions, the Se in selenocysteine is ionized and functionally serves as an effective and efficient biological catalyst in a number of physiological processes. It is fundamentally and functionally important to human health because it is a primary component of many metabolic pathways, such as antioxidant defense system, immune function, and thyroid hormone metabolism that are required for normal physiological activities in cells.[9] Because of the health importance of Se, its insufficiency has been associated with some human disease conditions including cancer, diabetes, cardiovascular diseases, and immune system disorders. Se has shown prospect against the detrimental activity of oxidative stress mediated by oxidative radicals. It can preserve biomolecular integrity against lipid peroxidation (LPO).[9],[10] Furthermore, there are growing reports on the possible benefits of Se against xenobiotic-induced toxicities. Its supplementation was shown to protect against chlorpyrifos-induced hepatotoxicity in rats [11] and silver nanoparticle-induced hepatotoxicity in rats.[12] In addition, it has restored hepatic architecture in galactosamine-induced hepatotoxicity in rats.[13] However, there is information gap on the protective effect of Se against INH-RIF-induced hepatotoxicity in animal models. This study assessed if Se supplementation could protect against hepatotoxicity induced by INH-RIF in albino rats.


  Materials and Methods Top


Animals and chemicals

The experimental procedure was approved by the Research Ethics Committee of the Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Nigeria. Forty-five adult male albino rats (220–260 g) randomly assigned to four groups were used. The albino rats were obtained from the animal breeding facility of the Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Nigeria. The rats were kept in cages of n = 5 at room temperature and natural light cycle with ad libitum access to water and standard diet. The rats were allowed to acclimatize for 2 weeks before the commencement of the study. Se capsule (Sodium selenite) used was manufactured by Bactolac Pharmaceuticals Inc., 7 Oser Avenue, Hauppauge, USA. INH-RIF table used was manufactured by Oxalis Labs, Baddi, Kharuni, Himachal Pradesh, India. All other chemicals used are of analytical grade.

Experimental design

  • Group 1A (Placebo control) was orally treated with normal saline (0.2 mL), whereas group 1B (Solvent control) was orally treated with corn oil (0.2 mL) daily for 21 days
  • Group 2 (2A–2C) was orally treated with Se (0.1, 0.2, and 0.4 mg/kg)[14] dissolved in corn oil daily for 21 days
  • Group 3 was orally treated with INH-RIF (50/100 mg/kg)[15] dissolved in normal saline daily for 21 days
  • Group 4 (4A–4C) was orally treated with Se (0.1 mg/kg) + INH-RIF (50/100 mg/kg), Se (0.2 mg/kg) + INH-RIF (50/100 mg/kg), and Se (0.4 mg/kg) + INH-RIF (50/100mg/kg) daily for 21 days.


Animal sacrifice

At the end of treatment, the rats were fasted overnight and sacrificed under diethyl ether anesthesia. Whole blood samples were collected through cardiac puncture and were allowed to clot. The clots were centrifuged at 1500 g for 15 min, and serum samples were separated for biochemical evaluations. The rats were sectioned; liver samples were excised and immediately rinsed in cold saline. The rinsed liver samples were homogenized in 0.1 M Tris-HCl buffer, pH 7.4 and centrifuged at 1200 g for 15 min. The supernatants were decanted and assessed for biochemical indices.

Evaluation of biochemical parameters

Serum and liver alkaline phosphatase (ALP), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), total bilirubin (TB), and conjugated bilirubin (CB) levels were analyzed using commercial test kits (Randox Laboratories Ltd., UK). Liver malondialdehyde (MDA) was assessed using the method of Buege and Aust, 1978.[16] Superoxide dismutase (SOD) was assayed according to Sun and Zigman, 1978.[17] Catalase (CAT) was assayed as described by Aebi, 1984.[18] Glutathione peroxidase (GPx) was measured using the method of Rotruck et al. 1973,[19] whereas glutathione (GSH) was determined as reported by Sedlak and Lindsay, 1968.[20]

Histological assessment of the liver

At the end of treatment, liver samples were collected from all the groups and fixed in 10% buffered neutral formalin. The liver samples were dehydrated in ascending grades of ethyl alcohol and mounted in paraffin block. Five-μm sections were obtained, stained with hematoxylin and eosin, and examined for structural changes under a light microscope.

Statistical analysis

Means and standard error of means were calculated from the five replicates per group. Results were analyzed using one-way analysis of variance (ANOVA) followed by Tukey's post hoc test with the aid of GraphPad Prism Version 5.01 (Software Inc., La Jolla, California, U.S.A.). A P < 0.05, 0.01, and 0.001 was considered statistically significant.


  Results Top


Effects on body and liver weights and liver function indices

Normal (P > 0.05) body and liver weights were observed in rats treated with Se, but significant (P < 0.01) increase in liver weight with significant (P < 0.01) decrease in body weight occurred in rats treated with INH-RIF when compared to control [Table 1]. However, pretreatment with Se significantly (P < 0.01) restored liver and body weights when compared to treatment with INH-RIF [Table 1]. In Se-treated rats, serum AST, ALT, ALP, GGT CB, TB, and LDH levels were not significantly (P > 0.05) different when compared to control [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]. On the other hand, treatment with INH-RIF significantly (P < 0.001) increased serum AST, ALT, ALP, GGT CB, TB, and LDH levels to 195 ± 12.1, 74.0 ± 5.37, 79.9 ± 5.90, 0.84 ± 0.04, 10.9 ± 1.09, 11.1 ± 0.72, and 81.2 ± 6.51, respectively, when compared to control [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]. The aforementioned increases represent 644.9%, 413.1%, 363.0%, 475.0%, 317.1%, 293.9%, and 408.8%, respectively [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]. However, serum AST, ALT, ALPT, GGT CB, TB, and LDH levels were significantly reduced in a dose-dependent fashion in rats pretreated with Se 0.1 mg/kg (P < 0.05), Se 0.2 mg/kg (P < 0.01), and Se 0.4 mg/kg (P < 0.001) when compared to INH-RIF [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7].
Table 1: Effects of selenium on body and liver weights of isoniazid-rifampicin-treated albino rats

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Figure 1: Activity of Se on serum ALT level of rats treated with INH-RIF. Data are expressed as mean ± SEM, n = 5. #P < 0.001 when compared to control, *P < 0.05 when compared to INH-RIF, **P < 0.01 when compared to INH-RIF, ***P < 0.001 when compared to INH-RIF. Se = Selenium, INH-RIF = Isoniazid-rifampicin, ALT = Alanine aminotransferase, SEM = Standard error of the mean

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Figure 2: Activity of Se on serum AST level of rats treated with INH-RIF. Data are expressed as mean ± SEM, n = 5. #P < 0.001 when compared to control, *P < 0.05 when compared to INH-RIF, **P < 0.01 when compared to INH-RIF, ***P < 0.001 when compared to INH-RIF. Se = Selenium, INH-RIF = Isoniazid-rifampicin, AST = Aspartate aminotransferase, SEM = Standard error of mean

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Figure 3: Activity of Se on serum ALP level of rats treated with INH-RIF. Data are expressed as mean ± SEM, n = 5. #P < 0.001 when compared to control, *P < 0.05 when compared to INH-RIF, **P < 0.01 when compared to INH-RIF, ***P < 0.001 when compared to INH-RIF. Se = Selenium, INH-RIF = Isoniazid-rifampicin, ALP = Alkaline phosphatase, SEM = Standard error of the mean

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Figure 4: Activity of selenium on serum GGT level of rats treated with INH-RIF. Data are expressed as mean ± SEM, n = 5. #P < 0.001 when compared to control, *P < 0.05 when compared to INH-RIF, **P < 0.01 when compared to INH-RIF, ***P < 0.001 when compared to INH-RIF. Se = Selenium, INH-RIF = Isoniazid-rifampicin, SEM = Standard error of the mean, GGT = Gamma-glutamyl transferase

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Figure 5: Activity of Se on serum LDH level of rats treated with INH-RIF. Data are expressed as mean ± SEM, n = 5. #P < 0.001 when compared to control, *P < 0.05 when compared to INH-RIF, **P < 0.01 when compared to INH-RIF, ***P < 0.001 when compared to INH-RIF. Se = Selenium, INH-RIF = Isoniazid-rifampicin, SEM = Standard error of the mean, LDH = Lactate dehydrogenate

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Figure 6: Activity of Se on serum TB level of rats treated with INH-RIF. Data are expressed as mean ± SEM, n = 5. #P < 0.001 when compared to control, *P < 0.05 when compared to INH-RIF, **P < 0.01 when compared to INH-RIF, ***P < 0.001 when compared to INH-RIF. Se = Selenium, INH-RIF = Isoniazid-rifampicin, SEM = Standard error of the mean, TB = Total bilirubin

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Figure 7: Activity of Se on serum CB level of rats treated with INH-RIF. Data are expressed as mean ± SEM, n = 5. #P < 0.001 when compared to control, *P < 0.05 when compared to INH-RIF, **P < 0.01 when compared to INH-RIF, ***P < 0.001 when compared to INH-RIF. Se = Selenium, INH-RIF = Isoniazid-rifampicin, SEM = Standard error of the mean, CB = Conjugated bilirubin

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Effect on liver tissue biochemical parameters

AST, ALT ALP, GGT, and LDH levels in the liver tissues of rats treated with Se were normal (P > 0.05), but were significantly (P < 0.001) increased in rats treated with INH-RIF when compared to control [Table 2]. The observed increases in liver AST, ALT ALP, GGT, and LDH levels represent 332.1%, 296.2%, 294.3%, 271.0%, and 313.3%, respectively [Table 2]. However, the aforementioned parameters were significantly decreased in a dose-dependent fashion in rats pretreated with Se 0.1 mg/kg (P < 0.05), Se 0.2 mg/kg (P < 0.01), and Se 0.4 mg/kg (P < 0.001) when compared to rats treated with INH-RIF [Table 2].
Table 2: Effect of selenium on liver tissue biochemical parameters of isoniazid-rifampicin-treated rats

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Effects on liver oxidative stress indices and histology

Normal (P > 0.05) liver activities of GSH, CAT, GPx, SOD, and MDA were observed in rats treated with Se when compared to control [Table 3]. On the other hand, the activities of liver GSH, CAT, GPx, and SOD were significantly (P < 0.001) decreased whereas the activities of MDA were significantly (P < 0.001) increased in rats treated with INH-RIF when compared to control [Table 3]. However, the activities of GSH, CAT, GPx, and SOD were significantly increased whereas the activities of MDA were significantly decreased in a dose-dependent fashion in rats pretreated with Se 0.1 mg/kg (P < 0.05), Se 0.2 mg/kg (P < 0.01), and Se 0.4 mg/kg (P < 0.001) when compared to rats treated with INH-RIF [Table 3]. Furthermore, normal liver hepatocytes were observed in the control rats [Figure 8]a, whereas ischemic necrosis and vascular congestion were observed in the liver of rats treated with INH-RIF [Figure 8]b. The liver of rats pretreated with Se (0.1 mg/kg) showed centrilobular necrosis and inflammatory cells [Figure 8]c. However, the liver of rats pretreated with Se (0.2 mg/kg) showed normal hepatocytes [Figure 8]d. Also, the liver of rats pretreated with Se (0.4 mg/kg) showed normal hepatocytes [Figure 8]e.
Table 3: Effect of selenium on liver oxidative stress indices of isoniazid-rifampicin-treated rats

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Figure 8: (a) Control liver showing NH. (b) Liver of rat treated with INH-RIF (50/100 mg/kg) showing IN and VG. (c) Liver of rats pretreated with Se (0.1 mg/kg) and treated INH-RIF (50/100 mg/kg) showing CN and IC. (d) Liver of rats pretreated with Se (0.2 mg/kg) and treated with INH-RIF (50/100 mg/kg) showing NH. (e) Liver of rats pretreated with Se (0.4 mg/kg) and treated with INH-RIF (50/100 mg/kg) showing NH (H and E, ×400). NH = Normal hepatocyte, IN = Ischemic necrosis, VG = Vascular congestion, CN = Centrilobular necrosis, IC = Inflammatory cells, Se = Selenium, INH-RIF = Isoniazid-rifampicin

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  Discussion Top


The liver has numerous essential functions including detoxification, metabolic, biotransformation, and biosynthetic functions.[21] However, the hepatotoxic effect of drugs can impair liver functions, especially when the regenerative ability of the liver is compromised.[22] A number of mechanisms have been speculated by which drugs can cause hepatotoxicity with oxidative stress gaining more attention. This has created an enabling experimental environment where antioxidants are been screened for possible hepatoprotective effects.[23] This study screens Se for possible protective effect against hepatotoxicity induced by INH-RIF in albino rats. The estimations of serum biochemical markers (AST, ALT, ALP GGT, LDH, CT, and TB) are used to proffer reliable information on the hepatotoxic impact of drugs and other chemical agents. Higher serum levels of the aforementioned biochemical markers are clear indication that the liver has been assaulted.[24] Body and liver weights and biochemical markers measured in the serum and liver were stable in Se-treated rats. On the other hand, body weight was decreased whereas liver weight and biochemical markers measured in the serum and liver were elevated in rats treated with INH-RIF. The observation in rats treated with INH-RIF is an indication of hepatotoxicity which runs parallel with previous findings.[25] The hepatic insult caused by INH-RIF might have increased the cellular permeability of hepatocyte membrane culminating in the eventual leakage of the aforementioned biochemical markers into the blood. The observed decrease in body weight may be attributed to decreased appetite, whereas increase in liver weight may due to inflammation. The hepatotoxic impact of INH-RIF was reversed in a dose-dependent fashion in Se-pretreated rats marked by decreased levels of the biochemical markers measured in the serum and liver and restored liver and body weights.

The induction of oxidative stress by the excess activities of reactive oxidative species (ROS) can cause hepatocyte membrane damage with consequent alterations in liver function. Hepatocytes have antioxidants that down-regulate oxidative stress, but may be rendered ineffective amid overwhelming oxidative stress.[26] Stable liver antioxidants (CAT, SOD, GSH, and GPx) were noted in Se-treated rats, but were decreased in rats treated with INH-RIF. The observation in rats treated with INH-RIF runs parallel with previous findings.[27] However, Se pretreatment upregulated the activities of hepatic antioxidants in a dose-dependent fashion. This observation can be attributed to the inhibition of oxidative stress caused by INH-RIF and increased antioxidants syntheses by Se. Studies have shown that Se is incorporated in the active sites of some antioxidants including GPx and is essential for their syntheses and activities.[28] ROS-mediated peroxidation of biological molecules, especially lipids, has been associated with some disease conditions, such as rheumatoid arthritis, cardiovascular diseases, cancer, and inflammatory disorders. Several methods are used to assess ROS-induced LPO with the measurement of MDA as one of the primary methods. Increase in serum or cellular MDA concentration is always correlated with LPO.[29] Liver MDA levels were normal in Se-treated rats, but were upregulated in rats treated with INH-RIF. The upregulated MDA level caused by INH-RIF is an evident confirmation of LPO which is consistent with previous reports.[30] Furthermore, INH-RIF impacted negatively on the liver by altering hepatocyte histology characterized by ischemic necrosis and vascular congestion. This observation supports earlier findings.[31] However, the detrimental impact of INH-RIF on liver histology was reversed in Se-pretreated rats in a dose-dependent fashion. In this study, the ability of Se to restore biochemical markers and liver histology of rats treated with INH-RIF is a vivid indication of its potential hepatoprotective activity that may have clinical application. The mechanism by which INH-RIF causes hepatotoxicity has been speculated to involve ROS and toxic intermediaries produced during INH biotransformation.[32] INH is biotransformed to toxic metabolites (acetyl hydrazine and hydrazine) by hepatic N-acetyltransferase and amidohydrolase.[33],[34] Acetyl hydrazine can produce reactive acetylating species which can covalently bind to hepatic proteins.[35] In addition, the hepatotoxic effect of hydrazine has been attributed to ROS-induced oxidative stress mediated by cytochrome P450 2E1 (CYP2E1). CYP2E1 has been associated with the production of free radicals which are speculated to be involved in INH-induced hepatotoxicity.[36.37] RIF is an essential inducer of CYP2E1 which can aggravate the hepatotoxic effect of INH by increasing the production of hydrazine.[38] Furthermore, studies have associated hepatotoxicity caused by INH-RIF with inflammation characterized by increased production of proinflammatory mediators.[39] In this study, Se might have protected against hepatotoxicity caused by INH-RIF through its activities against oxidative stress and inflammation. Se is an essential component of most antioxidants that are involved in scavenging and neutralization of excess free radicals.[40] It has the ability to safeguard cell integrity by preventing cellular components (lipids, proteins, and DNA) from oxidative stress-induced damage.[41] Furthermore, Se can inhibit inflammation by decreasing the production of proinflammatory mediators.[42]


  Conclusion Top


Se attenuates INH-RIF - induced hepatotoxicity in a dose-dependent fashion. Se may be clinically used as an adjuvant treatment for hepatotoxicity caused by INH-RIF.

Acknowledgments

We kindly appreciate Mr. Cosmos Obi of the Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Nigeria, for animal handling. The authors also appreciate Dr. Obuma Yibala of the Department of Medical Laboratory Science, Faculty of Basic Medical Sciences, Niger Delta University, Nigeria, for handling liver histology.

Financial support and sponsorship

Nil.

Conflicts of interest

The authors declare no conflicts of interest.



 
  References Top

1.
Abdel-Ghaffar O, Mahmoud ST, Said AA, Sanad FA. Hepatoprotective effect of rutin against oxidative stress of isoniazid in albino rats. Int J Pharmacol 2017;13:516-28.  Back to cited text no. 1
    
2.
Gajalakshmi V, Peto R, Kanaka TS, Jha P. Smoking and mortality from tuberculosis and other diseases in India: Retrospective study of 43000 adult male deaths and 35000 controls. Lancet 2003;362:507-15.  Back to cited text no. 2
    
3.
Raviglione M, Sulis G. Tuberculosis 2015: Burden, challenges and strategy for control and elimination. Infect Dis Rep 2016;8:6570.  Back to cited text no. 3
    
4.
Sturkenboom MG. Clinical Pharmacology and Therapeutic Drug Monitoring ofFirst-Line Anti-Tuberculosis Drugs. University of Groningen: Ridderprint BV, Netherlands; 2016. Available from: http://www.rug.nl/research/portal.  Back to cited text no. 4
    
5.
Makhlouf HA, Helmy A, Fawzy E, El-Attar M, Rashed HA. A prospective study of antituberculous drug-induced hepatotoxicity in an area endemic for liver diseases. Hepatol Int 2008;2:353-60.  Back to cited text no. 5
    
6.
Singh M, Sasi P, Gupta VH, Rai G, Amarapurkar DN, Wangikar PP. Protective effect of curcumin, silymarin and N-acetylcysteine on antitubercular drug-induced hepatotoxicity assessed in anin vitro model. Hum Exp Toxicol 2012;31:788-97.  Back to cited text no. 6
    
7.
Nelson SD, Mitchell JR, Timbrell JA, Snodgrass WR, Corcoran GB 3rd. Isoniazid and iproniazid: Activation of metabolites to toxic intermediates in man and rat. Science 1976;193:901-3.  Back to cited text no. 7
    
8.
Sodhi CP, Rana SF, Attri S, Mehta S, Yaiphei K, Mehta SK. Oxidative-hepatic injury of isoniazid-rifampicin in young rats subjected to protein and energy malnutrition. Drug Chem Toxicol 1998;21:305-17.  Back to cited text no. 8
    
9.
Brown KM, Arthur JR. Selenium, selenoproteins and human health: A review. Public Health Nutr 2001;4:593-9.  Back to cited text no. 9
    
10.
Aksoy A, Karaoglu A, Akpolat N, Naziroglu M, Ozturk T, Karagoz ZK. Protective role of selenium and high dose Vitamin E against cisplatin-induced nephrotoxicty in rats. Asian Pac J Cancer Prev 2015;16:6877-82.  Back to cited text no. 10
    
11.
Heikal TM, El-Sherbiny M, Hassan SA, Arafa A, Ghanem HZ. Antioxidant effect of selenium on hepatotoxicity induced by chlorpyrifos in male rats. Int J Pharm Pharm Sci 2012;4:603-9.  Back to cited text no. 11
    
12.
Ansar S, Alshehri SM, Abudawood M, Hamed SS, Ahamad T. Antioxidant and hepatoprotective role of selenium against silver nanoparticles. Int J Nanomedicine 2017;12:7789-97.  Back to cited text no. 12
    
13.
Catal T, Tunali S, Bolkent S, Yanardag R. An antioxidant combination improves histopathological alterations and biochemical parameters in D-galactosamine-induced hepatotoxicity in rats. Eur J Biol 2017;76:14-9.  Back to cited text no. 13
    
14.
Atefifiahin A, Yilmaz S, Karahan I, Pirinçci I, Tafidemir B. The effects of Vitamin E and selenium on cypermethrin-induced oxidative stress in rats. Turk J Vet Anim Sci 2005;29:385-91.  Back to cited text no. 14
    
15.
Vuyyuri B, Bhagyalakshmi A, Rajyalakshmi R, Jagadeeswari S. Hepatoprotective activity of Canthium dicoccum in isoniazid and rifampicin induced hepatotoxicity. Inter J Pharm Clin Res 2015;7:239-45.  Back to cited text no. 15
    
16.
Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978;52:302-10.  Back to cited text no. 16
    
17.
Sun M, Zigman S. An improved spectrophotometric assay for superoxide dismutase based on epinephrine autoxidation. Anal Biochem 1978;90:81-9.  Back to cited text no. 17
    
18.
Aebi H. Catalase in vitro. In: Colowick SP, Kaplane NO, editors. Method in Enzymology. New York, USA: Academic Press; 1984.  Back to cited text no. 18
    
19.
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: Biochemical role as a component of glutathione peroxidase. Science 1973;179:588-90.  Back to cited text no. 19
    
20.
Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem 1968;25:192-205.  Back to cited text no. 20
    
21.
Chellappan DK, Ganasen S, Batumalai S, Candasamy M, Krishnappa P, Dua K, et al. The protective action of the aqueous extract of Auricularia polytricha in paracetamol induced hepatotoxicity in rats. Recent Pat Drug Deliv Formul 2016;10:72-6.  Back to cited text no. 21
    
22.
Xu L, Gao J, Wang Y, Yu W, Zhao X, Yang X, et al. Myrica rubra extracts protect the liver from CCl (4)-induced damage. Evid Based Complement Alternat Med 2011;2011:518302.  Back to cited text no. 22
    
23.
Medina J, Moreno-Otero R. Pathophysiological basis for antioxidant therapy in chronic liver disease. Drugs 2005;65:2445-61.  Back to cited text no. 23
    
24.
Wahid A, Hamed AN, Eltahir HM, Abouzied MM. Hepatoprotective activity of ethanolic extract of Salix subserrata against CCl4-induced chronic hepatotoxicity in rats. BMC Complement Altern Med 2016;16:263.  Back to cited text no. 24
    
25.
Tayal V, Kalra BS, Agarwal S, Khurana N, Gupta U. Hepatoprotective effect of tocopherol against isoniazid and rifampicin induced hepatotoxicity in albino rabbits. Indian J Exp Biol 2007;45:1031-6.  Back to cited text no. 25
    
26.
Singh N, Kamath V, Narasimhamurthy K, Rajini PS. Protective effect of potato peel extract against carbon tetrachloride-induced liver injury in rats. Environ Toxicol Pharmacol 2008;26:241-6.  Back to cited text no. 26
    
27.
Kumar V, Sharma A, Machawal L, Nagarajan K, Siddiqui SA. Effect of Centella asiatica against anti-tuberculosis drugs-induced hepatotoxicity: Involvement of mitochondria and oxidative stress. J Phytopharmacol 2014;3:310-15.  Back to cited text no. 27
    
28.
Rahmanto AS, Davies MJ. Selenium-containing amino acids as direct and indirect antioxidants. IUBMB Life 2012;64:863-71.  Back to cited text no. 28
    
29.
Södergren E, Cederberg J, Vessby B, Basu S. Vitamin E reduces lipid peroxidation in experimental hepatotoxicity in rats. Eur J Nutr 2001;40:10-6.  Back to cited text no. 29
    
30.
Sankar M, Rajkumar J, Sridhar D. Hepatoprotective activity of heptoplus on isoniazid and rifampicin induced liver damage in rats. Indian J Pharm Sci 2015;77:556-62.  Back to cited text no. 30
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31.
Mujahid M, Hussain T, Siddiqui HH, Hussain A. Evaluation of hepatoprotective potential of Erythrina indica leaves against antitubercular drugs induced hepatotoxicity in experimental rats. J Ayurveda Integr Med 2017;8:7-12.  Back to cited text no. 31
    
32.
Chowdhury A, Santra A, Bhattacharjee K, Ghatak S, Saha DR, Dhali GK. Mitochondrial oxidative stress and permeability transition in isoniazid and rifampicin induced liver injury in mice. J Hepatol 2006;45:117-26.  Back to cited text no. 32
    
33.
Sarich TC, Adams SP, Petricca G, Wright JM. Inhibition of isoniazid-induced hepatotoxicity in rabbits by pretreatment with an amidase inhibitor. J Pharmacol Exp Ther 1999;289:695-702.  Back to cited text no. 33
    
34.
Tafazoli S, Mashregi M, O'Brien PJ. Role of hydrazine in isoniazid-induced hepatotoxicity in a hepatocyte inflammation model. Toxicol Appl Pharmacol 2008;229:94-101.  Back to cited text no. 34
    
35.
Yue J, Peng R, Chen J, Liu Y, Dong G. Effects of rifampin on CYP2E1-dependent hepatotoxicity of isoniazid in rats. Pharmacol Res 2009;59:112-9.  Back to cited text no. 35
    
36.
Nicod L, Viollon C, Regnier A, Jacqueson A, Richert L. Rifampicin and isoniazid increase acetaminophen and isoniazid cytotoxicity in human HepG2 hepatoma cells. Hum Exp Toxicol 1997;16:28-34.  Back to cited text no. 36
    
37.
Yue J, Peng R. Does CYP2E1 play a major role in the aggravation of isoniazid toxicity by rifampicin in human hepatocytes? Br J Pharmacol 2009;157:331-3.  Back to cited text no. 37
    
38.
Tasduq SA, Kaiser P, Sharma SC, Johri RK. Potentiation of isoniazid-induced liver toxicity by rifampicin in a combinational therapy of antitubercular drugs (rifampicin, isoniazid and pyrazinamide) in Wistar rats: A toxicity profile study. Hepatol Res 2007;37:845-53.  Back to cited text no. 38
    
39.
Liu X, Zhao M, Mi J, Chen H, Sheng L, Li Y. Protective effect of bicyclol on anti-tuberculosis drug induced liver injury in rats. Molecules 2017;22. pii: E524.  Back to cited text no. 39
    
40.
Tapiero H, Townsend DM, Tew KD. The antioxidant role of selenium and seleno-compounds. Biomed Pharmacother 2003;57:134-44.  Back to cited text no. 40
    
41.
McKenzie RC, Arthur JR, Beckett GJ. Selenium and the regulation of cell signaling, growth, and survival: Molecular and mechanistic aspects. Antioxid Redox Signal 2002;4:339-51.  Back to cited text no. 41
    
42.
Gao X, Zhang Z, Li Y, Hu X, Shen P, Fu Y, et al. Selenium deficiency deteriorate the inflammation of S. aureus infection via regulating NF-κB and PPAR-γ in mammary gland of mice. Biol Trace Elem Res 2016;172:140-7.  Back to cited text no. 42
    


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