Hepatoprotective effect of Hydro-alcohol extract of Mimusops elengi root against antitubercular drug-induced hepatotoxicity in rats

Prakash Dabadi¹, Fouad Saleih Resq AL-Suede^2,3*, Chandrashekhar VM^4*, Mallappa Shalavadi ⁴ , Ashok Gnanasekaran⁵

Development of therapeutics for the treatment of hepatotoxicity and oxidative stress  induced by ATDs

Abstract

Introduction: Nowadays, different chemicals and drugs are causing liver injuries including first-line antitubercular drugs (ATDs). There is a need to find safe and potent moieties of hepatoprotective drugs against liver diseases from different natural resources including medicinal plants. So, the current study aimed to evaluate the hepatoprotective property of Mimusops elengi root. Methodology: Mimusops elengi root extract (200-400mg/kg) was evaluated in an induced hepatotoxicity model of oxidative stress in Wistar rats by ATDs orally for 14 days. Markers indicating oxidative stress and hepatic damage such as serum transaminase (SGOT / SGPT), and alkaline phosphatase (ALP) were measured. Biomarkers of antioxidant status, superoxide dismutase, catalase, glutathione reductase, and marker of lipid peroxidation, were evaluated using standard procedures. The hematological lipid profile, bilirubin, glucose, and histopathological examination were also assessed. Results: intoxication with ATDs markedly reduced the hematological indices and elevated the biochemical enzyme markers (SGOT, SGPT, ALP p<0.001) and lipid profile (p<0.001), decreased and glucose was elevated. However, pretreatment with Mimusops elengi root extract significantly (p<0.001, p<0.01) improved this alteration and sustained the antioxidant potential. The Histopathological and biochemical data support hepatoprotective action. Conclusion: The results of the current study reinforced the extract of Mimusops elengi possesses significant hepatoprotective and antioxidant activity against ATDs- induced hepatotoxicity.

Keywords:  Hepatoprotective, Mimusops elengi, Isoniazid, Rifampicin, Anti-TB.

References

Akhtar, Nida, Ali, Mohd, & Alam, Mohd Sarwar. (2010). Gallic acid esters from the stem bark of Mimusops elengi L. Natural product research, 24(10), 962-972.

Al-Suede, Foaud Saleih R, Farsi, Elham, Ahamed, Mohamed Khadeer B, Ismail, Zhari, Majid, Aman S Abdul, & Majid, AMSA. (2014). Marked antitumor activity of cat’s whiskers tea (Orthosiphon stamineus) extract in orthotopic model of human colon tumor in nude mice. J Biochem Technol, 3(5), S170-176.

Al-Suede, Fouad Saleih R, Khadeer Ahamed, Mohamed B, Abdul Majid, Aman S, Baharetha, Hussin M, Hassan, Loiy EA, Kadir, Mohd Omar A, . . . Abdul Majid, Amin. (2014). Optimization of cat’s whiskers tea (orthosiphon stamineus) using supercritical carbon dioxide and selective chemotherapeutic potential against prostate cancer cells. Evidence-Based Complementary and Alternative Medicine, 2014.

Al-Suede, Fouad Saleih R.; Ahamed, Mohamed B. Khadeer; Abdul Majid, Aman S.;  Saghir, Sultan Ayesh Mohammed; Oon, Chern E.; Abdul Majid, Amin Malik Shah. . (2021). Immunomodulatory and Antiangiogenic Mechanisms of Polymolecular Botanical Drug Extract C5OSEW5050ESA OS Derived from Orthosiphon stamineus. Journal of Angiotherapy, , 5(1), 194-206.

Anbarasu, C, Rajkapoor, B, & Kalpana, J. (2011). Protective effect of Pisonia aculeata on Rifampicin and Isoniazid induced hepatotoxicity in rats. International Journal of Phytomedicine, 3(1), 75.

Anoopa, John L, Kannappan, N, & Manojkumar, P. (2020). Evaluation of Hepatoprotective activity in methanolic extract of Aerial parts of Hibiscus surattensis. Research Journal of Pharmacy and Technology, 13(10), 4635-4640.

Baliga, Manjeshwar Shrinath, Pai, Ramakrishna J, Bhat, Harshith P, Palatty, Princy Louis, & Boloor, Rekha. (2011). Chemistry and medicinal properties of the Bakul (Mimusops elengi Linn): A review. Food Research International, 44(7), 1823-1829.

Basini, J, Mohanalakshmi, S, & Anitha, K. (2013). Protective effect of Mirabilis jalapa leaves on anti-tuberculous drug-induced hepatotoxicity. Asian Journal of Pharmaceutical and Clinical Research, 6, 221-224.

Begum, Aisha, Parveen, Uzma, Sultana, Safura, Fatima, Nausheen, & Fareedullah, Mohd. (2020). Antitubercular Drug induced Hepatitis: An Adverse Drug Reaction. Indian Journal of Pharmacy Practice, 13(3).

Braughler, J Mark, Chase, Robin L, & Pregenzer, Jeffery F. (1987). Oxidation of ferrous iron during peroxidation of lipid substrates. Biochimica et Biophysica Acta (BBA)-Lipids and Lipid Metabolism, 921(3), 457-464.

Dabadi, Prakash, Chandrashekhar, VM, & Shalavadi, Mallappa. (2021). Phytochemical Screening and in vitro Free Radical Scavenging Activity of Hydroalcohol Extract of Mimusops elengi L. Root. RGUHS Journal of Pharmaceutical Sciences, 11(2).

Eminzade, Sude, Uras, Fikriye, & Izzettin, Fikret V. (2008). Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals. Nutrition & Metabolism, 5(1), 1-8.

Huang, Yi-Shin, Chern, Herng-Der, Su, Wei-Juin, Wu, Jaw-Ching, Chang, Shi-Chuan, Chiang, Chi-Huei, . . . Lee, Shou-Dong. (2003). Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis. Hepatology, 37(4), 924-930.

Jain, Avijeet, Soni, Manish, Deb, Lokesh, Jain, Anurekha, Rout, SP, Gupta, VB, & Krishna, KL. (2008). Antioxidant and hepatoprotective activity of ethanolic and aqueous extracts of Momordica dioica Roxb. leaves. Journal of ethnopharmacology, 115(1), 61-66.

Malviya, Neelesh, Jain, Sanjay, Jain, Avnish, Jain, Sourabh, & Gurjar, Rajenda. (2010). Evaluation of in vitro antioxidant potential of aqueous extract of Trapa natans L. fruits. Acta Poloniae Pharmaceutica, 67(4), 391-396.

Metushi, IG, Cai, P, Zhu, X, Nakagawa, T, & Uetrecht, JP. (2011). A fresh look at the mechanism of isoniazid-induced hepatotoxicity. Clinical Pharmacology & Therapeutics, 89(6), 911-914.

Misra, H, & Greenwald, RA. (1985). CRC handbook of methods for oxygen radical research. CRC Press, Boca Raton, 237-247.

Molla, Yalew, Wubetu, Muluken, & Dessie, Bekalu. (2021). Anti-tuberculosis drug induced hepatotoxicity and associated factors among tuberculosis patients at selected hospitals, Ethiopia. Hepatic Medicine: Evidence and Research, 13, 1.

Moron, Maria S, Depierre, Joseph W, & Mannervik, Bengt. (1979). Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochimica et biophysica acta (BBA)-general subjects, 582(1), 67-78.

Ohno, M, Yamaguchi, I, Yamamoto, I, Fukuda, T, Yokota, S, Maekura, R, . . . Maeda, K. (2000). Slow N-acetyltransferase 2 genotype affects the incidence of isoniazid and rifampicin-induced hepatotoxicity. The International Journal of Tuberculosis and Lung Disease, 4(3), 256-261.

Pari, L, & Kumar, N Ashok. (2002). Hepatoprotective activity of Moringa oleifera on antitubercular drug-induced liver damage in rats. Journal of Medicinal Food, 5(3), 171-177.

Prabhakar, KR, Veerapur, VP, Parihar, K Vipan, Priyadarsini, KI, Rao, BSS, & Unnikrishnan, MK. (2006). Evaluation and optimization of radioprotective activity of Coronopus didymus Linn. in γ-irradiated mice. International journal of radiation biology, 82(8), 525-536.

Prakash, D, Koti, BC, Vijay, T, & Chandrakala, Katagi MS. (2011). Antiulcer activity of Mimusops elengi bark extracts against serotonin induced ulcer in rats. Int Res J Pharm, 2(8), 173-176.

Ramappa, Vidyasagar, & Aithal, Guruprasad P. (2013). Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management. Journal of clinical and experimental hepatology, 3(1), 37-49.

Remirez, Diadelis, Commandeur, Jan NM, Groot, Ed, & Vermeulen, Nico PE. (1995). Mechanism of protection of lobenzarit against paracetamol-induced toxicity in rat hepatocytes. European Journal of Pharmacology: Environmental Toxicology and Pharmacology, 293(4), 301-308.

Saram, GR, Imanuel, C, Kailasam, S, Narayana, ASL, & Venkatesan, P. (1986). Rifampin–induced release of hydrazine from isoniazid. A possible cause of hepatitis during treatment of tuberculosis with regiments containing isoniazid and rifampin. Am Rev Dis, 133, 1072-1075.

Singh, Charan, Jodave, Laxmikant, Bhatt, Tara Datt, Gill, Manjinder Singh, & Suresh, Sarasija. (2014). Hepatoprotective agent tethered isoniazid for the treatment of drug-induced hepatotoxicity: Synthesis, biochemical and histopathological evaluation. Toxicology reports, 1, 885-893.

Singh, Divya, Cho, William C, & Upadhyay, Ghanshyam. (2016). Drug-induced liver toxicity and prevention by herbal antioxidants: an overview. Frontiers in physiology, 6, 363.

Tabana, Yasser M, Al-Suede, Fouad Saleih R, Ahamed, Mohamed B Khadeer, Dahham, Saad S, Hassan, Loiy E Ahmed, Khalilpour, Saba, . . . Majid, Amin Malik Shah Abdul. (2016). Cat’s whiskers (Orthosiphon stamineus) tea modulates arthritis pathogenesis via the angiogenesis and inflammatory cascade. BMC complementary and alternative medicine, 16(1), 1-11.

Tandon, Vishal R, Khajuria, V, Kapoor, B, Kour, D, & Gupta, S. (2008). Hepatoprotective activity of Vitex negundo leaf extract against anti-tubercular drugs induced hepatotoxicity. Fitoterapia, 79(7-8), 533-538.

Tostmann, Alma, Boeree, Martin J, Aarnoutse, Rob E, De Lange, Wiel CM, Van Der Ven, Andre JAM, & Dekhuijzen, Richard. (2008). Antituberculosis drug-induced hepatotoxicity: concise up-to-date review. Journal of gastroenterology and hepatology, 23(2), 192-202.

Varley, Harold. (1980). Practical Clinical Biochemistry, vol. 1, William & Hieneman: Medical Books Ltd., London.

Yew, Wing Wai, & Leung, Chi Chiu. (2006). Antituberculosis drugs and hepatotoxicity. Respirology, 11(6), 699-707.