Biochemical effects of chronic administration of efavirenz on the intracranial auditory relay centers of adult Wistar rats

Adjene, Josiah Obaghwarhievwo; Avbunudiogba, John Afokoghene; Awhin, Prosper Ejiro; Igbigbi, Patrick Sunday

doi:10.1016/j.gmbhs.2012.10.002

Cited by 6 publications

(8 citation statements)

References 20 publications

(9 reference statements)

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“…They reported EFV up-regulation of hepatic endoplasmic reticulum (ER), oxidative stress markers and induction of morphological changes in ER [55]. Also, Adjene and colleagues have implicated EFV in oxidative stress induction through increased malondialdehyde level and down-regulation of antioxidants [56]. In this present study, elevated levels of transaminases can be correlated with histopathological damage observed in the liver of animals treated with these agents.…”

Section: Discussionsupporting

confidence: 65%

Hepatotoxic Assessment of Co-treatment with Isoniazid and Efavirenz in Albino Rats

Adikwu¹,

Nelson²,

Obele³

et al. 2015

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This study comparatively investigated the toxicological effects of treatment with efavirenz, isoniazid and efavirenz-isoniazid (EFV-INH) combination on liver function parameters and histology of adult male albino rats. Animals used in this study were divided into five (5) groups A-E of sixteen (16) animals each. Animals in group A (placebo control) were treated with water while animals in group B (solvent control) were treated with arachis oil orally. Animals in groups C-E were treated orally with 15mg/kg of INH, 10mg/kg of EFV and a combination of INH-EFV for 2-8 weeks respectively. At the end of drug therapy, serum was extracted from centrifuged blood sample and evaluated for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total and conjugated bilirubin. Animals were sacrificed and liver was harvested, weighed and evaluated for histopathological changes. Effects produced by co-treatment with EFV-INH on absolute liver weight, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, conjugated and total bilirubin were insignificant (p>0.05) when compared to effects produced by treatment with individual doses of EFV and INH. Histopathological evaluation of the liver of animals treated with EFV-INH combination showed vascular congestion, inflammation of parenchyma and hepatocytes degeneration. These results show that co-therapy with EFV-INH in patients with human immunodeficiency virus /tuberculosis co-infection may not be associated with synergistic hepatotoxicity.

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Section: Discussionsupporting

confidence: 65%

Hepatotoxic Assessment of Co-treatment with Isoniazid and Efavirenz in Albino Rats

Adikwu¹,

Nelson²,

Obele³

et al. 2015

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“…These finding are consistent with previous reports. [40][41][42] AST and ALT are enzymes involved in the transfer of amino groups of aspartate and alanine to ketoglutaric acid. 43 AST, ALT and ALP are present in the liver but, ALT is primarily located in the liver, and thus is a more specific marker of hepatocellular cell injury.…”

Section: Discussionmentioning

confidence: 99%

Antioxidants as recipes for efavirenz-induced liver damage: A study in albino rats

Adikwu

Bokolo

2018

J. contemp. med. sci.

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Objective Hepatotoxicity is a clinical challenge associated with the use of efavirenz (EFV). This study investigated the effects of n-acetylcysteine (NAC), vitamins C and E on EFV-induced hepatotoxicity in albino rats. Methods Rats were divided into groups and administered with NAC (20 mg/kg), vitamin C (50 mg/kg), vitamin E (50 mg/kg), vitamins C + E and 60 mg/kg of EFV, respectively. Rats were also divided into groups and pretreated with NAC, vitamins C, E, and combined doses of vitamins C + E prior to treatment with EFV for 15 days, respectively. After drug administration rats were sacrificed and serum was collected and evaluated for liver function parameters. Rats were dissected, liver was collected weighed and, homogenized and evaluated for alkaline phosphatase (ALP), alanine aminotransferase (AST), aspartate aminotransferase (ALT), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), malondialdehyde (MDA), super oxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPX) levels and pathological damage. Results Effects were not significant (p > 0.05) on body and liver weights, however, the levels of AST, ALT, AST, GGT, LDH, CB, TB and MDA were increased significantly (P < 0.05) whereas SOD, CAT, SOD, GSH and GPX were decreased significantly (P < 0.05) in EFV-treated rats in comparison to control. The liver of EFV-treated rats showed necrosis of hepatocytes hepatocytes necroses. Nevertheless, EFV-induced alterations in the above parameters were significantly (P < 0.05) ameliorated in antioxidants pretreated rats. The combined doses of vitamins C and E producedbest and significant (P < 0.05) in comparison to their individual doses. Conclusion This study shows the showed prospects of antioxidants as candidates for the treatments of efavirenz-induced hepatotoxicity.

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“…Zidovudine and indinavir are known to be associated associate with some cardiovascular effects eg atherosclerosis which could be attributed to oxidative stress (Jiang et al, 2007;2009). Efavirenz which is known to be associated with central nervous system disorders was reported to induce oxidative stress in the intracranial visual relay centers of adult wistar rats (Adjene et al, 2011). Efevirenz has also shown evidence for the involvement of mitochondrial dysfunction and oxidative stress in its cellular toxicity in animals (Apostolova et al, 2010).…”

Section: Antiretroviral Induced Oxidative Stress In Animalsmentioning

confidence: 99%

Antiretroviral Toxicity and Oxidative Stress

Adikwu

Nelson

Oputiri

et al. 2013

American Journal of Pharmacology and Toxicology

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Antiretroviral drugs are used for the treatment of human immunodeficiency virus, they are used as combination regimens to achieve the highest possible benefit, tolerability, compliance and to diminish the risk of resistance development. Reports from preclinical and clinical studies have linked antiretrovirals with some toxicological effects which could be associated with redox imbalance (oxidative stress). This stimulated us to review relevant literature on the relationship between antiretroviral induced toxicological effects and redox imbalance. Available literature on antiretroviral associated toxicological effects and oxidative stress were comprehensively reviewed. Literature showed that antiretrovirals are associated with toxicological effects which includes hepatotoxicity, cardiotoxicity, hematotoxicity and nephrotoxicity. Reports in animal studies also showed that these toxicological effects could be associated with oxidative stress through the generation of oxidative radicals, depletion of antioxidants and antioxidant enzymes leading to mitochondria damage in the heart, kidney, liver brain and other organs. In humans, studies also showed that antiretrovirals are associated with lipid peroxidation, depletion of antoxidants and antioxidant enzymes which are elements of oxidative stress. Furthermore it was observed that supplementations with some antioxidants mitigated antiretroviral induced oxidative stress, mitochondria damage and toxicological effects. Antiretroviral drugs are associated with toxicological effects which may involve redox imbalance, but more studies are required to correlate antiretroviral toxicities with oxidative stress.

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Biochemical effects of chronic administration of efavirenz on the intracranial auditory relay centers of adult Wistar rats

Cited by 6 publications

References 20 publications

Hepatotoxic Assessment of Co-treatment with Isoniazid and Efavirenz in Albino Rats

Hepatotoxic Assessment of Co-treatment with Isoniazid and Efavirenz in Albino Rats

Antioxidants as recipes for efavirenz-induced liver damage: A study in albino rats

Antiretroviral Toxicity and Oxidative Stress

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