article · Evidence-based Complementary and Alternative Medicine
Paclitaxel is a widely used chemotherapy drug whose long-term application can cause serious liver toxicity. This research evaluated whether the flavonoids rutin and hesperidin, administered alone or together, could shield male Wistar rats from paclitaxel-induced liver damage over a six-week regimen. Administering rutin, hesperidin, or their combination significantly lessened liver injury markers, including elevated serum enzymes, bilirubin, and lipid peroxidation, while improving protective antioxidant levels such as glutathione and superoxide dismutase. The interventions also ameliorated severe structural liver damage, suppressed the pro-apoptotic marker caspase-3, and lowered the pro-inflammatory cytokine tumour necrosis factor-alpha. The combined administration of both compounds proved the most effective strategy for preserving liver function and structural integrity, operating through combined antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.
Paclitaxel is a cornerstone cancer therapy, but its clinical utility is often constrained by severe liver damage. Finding protective compounds that counteract this organ toxicity could eventually allow cancer patients to tolerate chemotherapy better. Demonstrating that natural flavonoids like rutin and hesperidin alleviate tissue damage, inflammation, and cellular death highlights a promising pathway for safer therapeutic strategies.
This work could interest pharmaceutical and nutraceutical developers seeking adjuvant therapies to protect oncology patients undergoing chemotherapy. Potential users would eventually be clinical oncologists and patients receiving paclitaxel. However, because the findings derive exclusively from an in vivo animal model, the research remains at an early laboratory stage and is far from direct clinical or commercial use, requiring subsequent toxicity profiling and human trials.
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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.
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DOI: 10.1155/2023/2738351
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