Attenuation of anti-tuberculosis therapy induced hepatotoxicity bySpirulina fusiformis, a candidate food supplement

Abstract

Therapy using Isoniazid (INH) and Rifampicin (RIF) leads to induction of hepatotoxicity in some individuals undergoing anti-tuberculosis treatment. In this study, we assessed the effect of Spirulina fusiformis on INH and RIF induced hepatotoxicity in rats compared with hepatoprotective drug Silymarin. Induction of hepatotoxicity was measured by changes in the liver marker enzymes (aspartate transaminase, alanine transaminase, and alkaline phosphatase). The antioxidant status was also analyzed in liver tissue homogenate and plasma by measurement of superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, and lipid peroxidation levels. We also aimed to study the binding and interactions of the transcription factors Pregnane X Receptor (PXR) and Farnesoid X Receptor (FXR) with INH, RIF, and representative active compounds of Spirulina fusiformis by in silico methods. The administration of INH and RIF resulted in significant (p < 0.05) decrease in the antioxidant levels and total protein levels. There was also a significant (p < 0.05) increase in the levels of liver marker enzymes. Spirulina fusiformis was seen to protect the parameters from significant changes upon challenge with INH and RIF in a dose-dependent manner. This was corroborated by histological examination of the liver. The results of the in silico analyses further support the wet lab results.

Genetic Variations Associated with Anti-Tuberculosis Drug-Induced Liver Injury

“…In addition, people with hepatitis C virus (HCV) infection have an increased risk [15, 16]. Some compounds in fruits and food supplements can reduce the risk of AT-DILI due to their abilities to inhibit CYP2E1 activity [17] or to increase anti-oxidative activities [18–20]. …”

Absence of significant association between UGT2B4 genetic variants and the susceptibility to anti‐tuberculosis drug‐induced liver injury in a Western Chinese population

“…Many factors contribute to the variability of ATLI, including genetic (genetic variations), physiological (age,6 sex7 and race), pathological factors (liver diseases such as HBV/HCV infection8,9) and living habits (dietary compounds,10 smoking11 and alcohol intake12). With the advance of pharmacogenomics (PGx), more attention has been focused on using genomic variants in patient screening and therapy in cancer and other diseases.…”

“…Although few reports have established a direct link between ATLI risk and UGT2B4 polymorphism, anti‐TB drugs are known to show strong binding and interactions with the transcription factors FXR and can induce cholestatic liver damage by inhibiting its activation . 10,18 Ding Yan et al19 found that reducing the expression of FXR might decrease the expression of UGT2B4 , increase the synthesis of BA, weaken the detoxicating and transporting functions and therefore, mediate the development of cholestatic hepatitis. UGT2B4 was also found to be a novel target gene of the nuclear receptor peroxisome proliferator‐activated receptor alpha ( PPARα ), which might decrease bacterial load and reduce inflammatory responses during mycobacterial infection and along with FXR, induce BA glucuronidation 20,21.…”

Investigation of Hepatoprotective and Antioxidant Activity of Celosia argentea against Tissue Injury Caused by Rifampicin Administration

“…Though there is no suitable drug to weaken the hepatotoxicity effect of TB drugs presently [8], herbs are believed to possess potential hepatoprotective agents [9]. Some plant extracts have been shown to contain constituents that improved antioxidant status which is usually depleted during treatment with TB drugs [10,11]. Many synthetic antioxidants have been shown to produce toxic or mutagenic effects [12], therefore antioxidants from natural sources will be more appropriate for the prevention of TB drugs toxicity [13].…”