Doxorubicin (DXB) is one of the most commonly used anticancer agents for treating solid and hematological malignancies; however, DXB-induced cardiorenal toxicity presents a limiting factor to its clinical usefulness in cancer patients. Costunolide (COST) is a naturally occurring sesquiterpene lactone with excellent anti-inflammatory, antioxidant and antiapoptotic properties. This study evaluated the effect of COST on DXB-induced cardiorenal toxicity in rats. Rats were orally treated with COST for 4 weeks and received weekly 5 mg/kg doses of DXB for three weeks. Cardiorenal biochemical biomarkers, lipid profile, oxidative stress, inflammatory cytokines, histological and immunohistochemical analyses were evaluated. DXB-treated rats displayed significantly increased levels of lipid profiles, markers of cardiorenal dysfunction (aspartate aminotransferase, creatine kinase, lactate dehydrogenase, troponin T, blood urea nitrogen, uric acid and creatinine). In addition, DXB markedly upregulated cardiorenal malondialdehyde, tumor necrosis factor-α, interleukin-1β, interleukin-6 levels and decreased glutathione, superoxide dismutase and catalase activities. COST treatment significantly attenuated the aforementioned alterations induced by DXB. Furthermore, histopathological and immunohistochemical analyses revealed that COST ameliorated the histopathological features and reduced p53 and myeloperoxidase expression in the treated rats. These results suggest that COST exhibits cardiorenal protective effects against DXB-induced injury presumably via suppression of oxidative stress, inflammation and apoptosis.
Introduction
Diabetic peripheral neuropathy (DPN) is still one of the most prevailing complication of diabetes and it affects a huge diabetic population.
Boesenbergia rotunda
is a ginger species that has both culinary and medicinal applications. Recent studies have revealed that
B. rotunda
has potential applications in diabetes, pain and inflammatory related disorders. As such this study investigated the potential of
B. rotunda
extract (EBR) in attenuating DPN in rats.
Methods
DPN was induced in male Sprague Dawley rats using a combination of 30% fructose solution and streptozotocin (40 mg/kg). Afterwards diabetic rats were treated with EBR (100 and 400 mg/kg) for 5 weeks. DPN was assessed using thermal hyperalgesia, cold and mechanical allodynia and rotarod test, while nociceptive responses were assessed by formalin and acetic acid test. In addition, serum proinflammatory cytokine levels were determined using ELISA kits.
Results
EBR displayed hypoglycemic effect by significantly reducing the blood glucose concentration of treated diabetic rats, while simultaneously alleviating the reduced body weight. Furthermore, EBR markedly alleviated thermal hyperalgesia, cold and mechanical allodynic responses as well as ameliorated motor coordination in the treated diabetic rats. In addition, EBR significantly reduced nociceptive responses in the formalin and acetic acid test, as well as decreased serum levels of proinflammatory cytokines (TNF-α and IL-1β).
Conclusion
The results suggested that EBR exerted anti-inflammatory and anti-nociceptive effects, thus alleviating diabetic painful neuropathy.
Cisplatin (CISP) is one of the most commonly used drug for treating various cancers and solid tumours, however, its usage has been heavy restricted due to its deleterious side effects including peripheral neuropathy. Therefore, this study describes the anti-hyperalgesia and anti-allodynia effects of Tiliacora triandra (TTE) in CISP induced peripheral neuropathy. Peripheral neuropathy was established in rats by intraperitoneal injection of 2.5 mg/kg of CISP once a week for 4 weeks and the rats were concurrently treated with TTE (250 and 500 mg/kg, po) daily for 5 weeks. After the treatment, thermal hyperalgesia, motor coordination (rotarod test), mechanical allodynia, acetic acid writhing and formalin tests were evaluated. The rats were sacrificed and blood samples were collected for estimation of haematological parameters. TTE significantly restored motor coordination deficits induced by CISP and TTE-treated rats showed marked improvement in thermal/chemical hyperalgesia and mechanical allodynia. Additionally, treatment with TTE also increased haematological parameters including haemoglobin, platelet count, WBC and RBC compared to CISP-treated group. These findings demonstrated that TTE effectively ameliorated CISP induced peripheral neuropathic pain in a cisplatin paradigm.
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