Rutin and Hesperidin Revoke the Hepatotoxicity Induced by Paclitaxel in Male Wistar Rats via Their Antioxidant, Anti-Inflammatory, and Antiapoptotic Activities

Yasmine A Ali; Hanan A Soliman; Mohamed Abdel-Gabbar; Noha A Ahmed; Kandil A A Attia; Fatma M Shalaby; El-Shaymaa El-Nahass; Osama M Ahmed

doi:10.1155/2023/2738351

Rutin and Hesperidin Revoke the Hepatotoxicity Induced by Paclitaxel in Male Wistar Rats via Their Antioxidant, Anti-Inflammatory, and Antiapoptotic Activities

Evid Based Complement Alternat Med. 2023 May 26:2023:2738351. doi: 10.1155/2023/2738351. eCollection 2023.

Authors

Yasmine A Ali¹, Hanan A Soliman¹, Mohamed Abdel-Gabbar¹, Noha A Ahmed², Kandil A A Attia^{3

4}, Fatma M Shalaby^{5

6}, El-Shaymaa El-Nahass⁷, Osama M Ahmed²

Affiliations

¹ Biochemistry Department, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt.
² Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt.
³ Clinical Nutrition Department, College of Applied Medical Sciences, Jazan University, P.O. Box 114, Jazan 45142, Saudi Arabia.
⁴ Department of Evaluation of Natural Resources, Environmental Studies and Research Institute, El-Sadat City University, El-Sadat City 32897, Egypt.
⁵ Biology Department, Faculty of Science, King Khalid University, Abha, Saudi Arabia.
⁶ Department of Zoology, Faculty of Science, Mansoura University, Mansoura, Egypt.
⁷ Department of Pathology, Faculty of Veterinary Medicine, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt.

Abstract

Paclitaxel, one of the most effective chemotherapeutic drugs, is used to treat various cancers but it is exceedingly toxic when used long-term and can harm the liver. This study aimed to see if rutin, hesperidin, and their combination could protect male Wistar rats against paclitaxel (Taxol)-induced hepatotoxicity. Adult male Wistar rats were subdivided into 5 groups (each of six rats). The normal group was orally given the equivalent volume of vehicles for 6 weeks. The paclitaxel-administered control group received intraperitoneal injection of paclitaxel at a dose of 2 mg/Kg body weight twice a week for 6 weeks. Treated paclitaxel-administered groups were given paclitaxel similar to the paclitaxel-administered control group together with oral supplementation of rutin, hesperidin, and their combination at a dose of 10 mg/Kg body weight every other day for 6 weeks. The treatment of paclitaxel-administered rats with rutin and hesperidin significantly reduced paclitaxel-induced increases in serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transferase activities as well as total bilirubin level and liver lipid peroxidation. However, the levels of serum albumin, liver glutathione content, and the activities of liver superoxide dismutase and glutathione peroxidase increased. Furthermore, paclitaxel-induced harmful hepatic histological changes (central vein and portal area blood vessel congestion, fatty changes, and moderate necrotic changes with focal nuclear pyknosis, focal mononuclear infiltration, and Kupffer cell proliferation) were remarkably enhanced by rutin and hesperidin treatments. Moreover, the elevated hepatic proapoptotic mediator (caspase-3) and pro-inflammatory cytokine (tumor necrosis factor-α) expressions were decreased by the three treatments in paclitaxel-administered rats. The cotreatment with rutin and hesperidin was the most effective in restoring the majority of liver function and histological integrity. Therefore, rutin, hesperidin, and their combination may exert hepatic protective effects in paclitaxel-administered rats by improving antioxidant defenses and inhibiting inflammation and apoptosis.