Alleviation of first line antitubercular drugs induced hepatotoxicity nephrotoxicity and genotoxicity in wistar rats by ethanolic extract of Adhatodavasica and Andrographispaniculata

Abstract

Isoniazid, rifampicin and pyrazinamide are first-line anti-tubercular (anti-TB) drugs usedto treat tuberculosis. Thesedrugs not only effective treatment against tuberculosisbut also liable for wide array of adverse drug reactions (ADRs),chieflyaffecting those organs involved in drug metabolism and excretion. ADRs related to anti-TB drugs are known due to high production of reactive oxygen species by the presence of their reactive metabolites. In the present study, anti-TB drugs elevated the oxidative and antioxidant enzymes levels, altered the hepato-renal marker enzymes and morphology of hepato-renal tissues. Anti-TB drugs mediated genotoxic perturbations were estimated by augmented DNA fragmentation in liver, increased frequency of micronucleation and chromosomal aberrations in bone marrow cells of Wistar rats. Furthermore, drugs exposure also troubled the expression levels of various xeno-metabolic genes. Adhatodavasica and Andrographispaniculata leave extract have to showed their amelioration by their anti-oxidative and free radical scavenging activity. The treatment with plant extract effectively reduced oxidative stress markers, boost up antioxidant enzymes levels, restored hepato-renal marker enzymes level and recuperated various morphological alterations induced by anti-TB drugs. Moreover, high dose treatment of both plant extracts reduced genotoxic burden and normalized xeno-metabolism. A. vasica and A. paniculata extract confers the hepato-protective, nephro-protective and geno-protective efficacy due to their active phytoconstituents that are exalted with anti-oxidative and free radical scavenging activity. Thus, this data suggests that these plant extracts could be explored for the potential pharmacological candidates that are actually effective against anti-TB drugs induced toxicities. newline