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

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.

Phytochemical Analysis, Antioxidant, Analgesic, Anti-Inflammatory, Hemagglutinin and Hemolytic Activities of Chemically Characterized Extracts from Origanum grosii (L.) and Thymus pallidus (L.)

“…Hesperidin, detected in relatively high amounts in the T. pallidus extract, has a well-documented history of exhibiting potent antioxidant properties. Moreover, numerous studies have reported its efficacy in attenuating inflammatory responses [13]. These findings indicate that thyme may hold promise as an anti-inflammatory agent, particularly due to its high content of hesperidin.…”

Rheumatoid Arthritis Treatment Potential of Stearic Acid Nanoparticles of Quercetin in Rats

“…A Vernier caliper (Mitutoyo, Japan) was used to measure the ankle swelling (mm) in the paw due to the FCA injection every 7 days . Experimental animals were divided into five groups with six rats in each group as follows: Normal control (N) group: These animals received 0.9% NaCl solution as an oral vehicle and routine diet and water. Arthritic control (AC) group: The rats treated with the FCA model received oral vehicle 0.9% NaCl solution and normal feed and water for 28 days. Arthritic treated (H) group: RA rats received the quercetin suspension at a dosage of 15 mg/kg , and normal NaCl solution and a routine diet. Arthritic treated (ST) group: All the rats in this group after induction of rheumatoid arthritis received the quercetin-loaded nanoparticles in suspension form at a dose of 15 mg/kg. Dexamethasone-treated (H) group: The rheumatoid arthritis rats received the normal diet of water and dexamethasone suspension (at a dose of 0.3 mg per kilogram of rat weight). …”

“…Arthritic treated (H) group: RA rats received the quercetin suspension at a dosage of 15 mg/kg , and normal NaCl solution and a routine diet.…”

“…Therapeutic efficacy of the prepared SLNs was assessed by testing ankle swelling, biochemical and inflammatory biomarker levels, and histopathological analysis of the ankle joint …”

“…Quercetin possesses a potent anti-inflammatory effect . Quercetin, at low concentration, blocks the lipooxygenase pathway while, at high concentration, it blocks both the cyclooxygenase and lipooxygenase pathways . Quercetin is a poorly absorbed substance and has a very poor oral bioavailability.…”