Hepatoprotective role of neutrosecR on hepatic damage induced by combination of zidovudine and combined anti-tuberculous agents in rats. Awodele Olufunsho,Agbaje Esther O,Adesina Enitan A,Akintonwa Alade The Tokai journal of experimental and clinical medicine BACKGROUND:Advent of the HIV/AIDS pandemic has led to a dramatic increase in the number of TB cases worldwide. Availability of highly active antiretroviral therapy (HAART) has significantly improved the outcome of HIV/AIDS, in terms of prevention of opportunistic infections (OIs) as well as mortality however; liver toxicity is one of the most relevant adverse effects of antiretroviral therapy (ART). PURPOSE:In view of the inevitable use of zidovudine (a common ART) and antituberculous fixed-dose combination therapy (FDCs) in the management of HIV-TB co-infection and the resultant hepatotoxicity, this study was aimed to investigate the hepatoprotective role of neutrosec (a combination of aminoacid and vitamins) on the hepatotoxicity induced by co-administration of zidovudine and combined fixed dose antituberculous agents. METHOD:Twenty four rats were randomly allotted to four groups, consisting of the control, zidovudine plus fixed dose combined anti TB agents treated group, zidovudine plus fixed dose combined anti TB agents plus neutrosec treated group and neutrosec alone treated group. Therapeutic doses of zidovudine (8.5 mg/kg/day), fixed dose combined anti TB agents (25 mg/kg/day) and neutrosec (0.4 ml/kg/day) were administered to the animals via oral gavage, daily over 60 days. After 60 days, rats were sacrificed for internal macroscopic and histological examination of the liver. The liver enzyme parameters (AST, ALP, Total bilirubin, Total protein, Albumin) were determined using fully automated clinical chemistry analyzer (Hitachi 912, Boehringer Mannheim, Germany). Antioxidant enzymes activity and lipid peroxidation were determined according to standard procedures. RESULTS:The AST results showed a significant (p ≤ 0.05) decreased in the zidovudine plus anti-TB plus neutrosec treated group (125.50 ± 22.71) compared with zidovudine plus anti-TB treated group (399. 10 ± 0.45). It further showed non-significant decreased (p ≥ 0.05) in the ALP levels between the zidovudine plus anti TB treated group (317.10 ± 73.48) and the zidovudine plus anti TB plus neutrosec treated group (203.20 ± 35.97). There was a non-significant (p ≤ 0.05) decrease in the MDA level of the zidovudine plus anti-TB plus neutrosec treated group compared with the zidovudine plus anti-TB treated group. CONCLUSION:The hepatotoxic effect of zidovudine plus combined anti TB drugs which may be due to free radical generation was modulated by neutrosec.

Medical plant extracts and natural compounds with a hepatoprotective effect against damage caused by antitubercular drugs: A review. Jiménez-Arellanes María Adelina,Gutiérrez-Rebolledo Gabriel Alfonso,Meckes-Fischer Mariana,León-Díaz Rosalba Asian Pacific journal of tropical medicine Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and PubMed. 10.1016/j.apjtm.2016.10.010

[PERSISTENT DRUG-INDUCED LIVER DAMAGES IN PATIENTS WITH PULMONARY TUBERCULOSIS]. Tuberkulez i bolezni legkikh The authors discuss the problem associated with the severe, persistent course of drug-induced liver disease slightly responsive to traditional treatment in patients receiving antituberculous therapy. The objective of the study was to reveal the essence and causes of drug-induced liver damage characterized by its severe, persistent course, evident clinical and laboratory manifestations, and a weak response to traditional therapy and to develop diagnostic principles. The severe, persistent course of drug-induced liver disease slightly responsive to traditional therapy was shown to be caused by a few competitive pathological processes occurring in the liver rather than failures in the therapeutic and diagnostic process. Prognostic criteria for the severe, persistent course of drug-induced liver disease slightly responsive to traditional therapy have been developed. A diagnostic algorithm is proposed.

[The effect of runihol and exogenous S-adenosyl-L-methionine on the morphological pattern of the liver upon hepatotoxic exposure to reserve-series antituberculous drugs]. Sukhanov D S,Vinogradova T I,Zabolotnykh N V,Vasil'eva S N,Vitovskaia M L Arkhiv patologii Experiments on 160 male albino outbred rats investigated the hepatoprotective activity of S-adenosyl-L-methionine (SAM) and runihol in liver damage caused by subtoxic doses of reserve-series antituberculous drugs (ATD) (PASA, cycloserine, prothionamide) and their combination. It was established that a combination of ATDs had the maximum hepatotoxic activity, cycloserine had the least. There was evidence that SAM versus runihol had a more pronounced ability to correct ATD-induced evolving cytolysis syndrome. Histological study indicated that SAM and runihol also showed a marked hepatoprotective effect. When added to PASA, prothionamide, or a combination of ATDs, both drugs promoted recovery of the hepatic architectonics and a reduction in the prevalence of albuminous dystrophy. The use of SAM additionally led to activation of alterative processes in the hepatic parenchyma.