Thymoquinone Ameliorates Carfilzomib-Induced Renal Impairment by Modulating Oxidative Stress Markers, Inflammatory/Apoptotic Mediators, and Augmenting Nrf2 in Rats.

Chemotherapy-induced kidney damage is an emerging problem that restricts cancer treatment effectiveness. The proteasome inhibitor carfilzomib (CFZ) is primarily used to treat multiple myeloma and has been associated with severe renal injury in humans. CFZ-induced nephrotoxicity remains an unmet medical need, and there is an urgent need to find and develop a nephroprotective and antioxidant therapy for this condition. Thymoquinone (TQ) is a bioactive compound that has been isolated from Nigella sativa seeds. It has a wide range of pharmacological properties. Therefore, this experimental design aimed to study the effectiveness of TQ against CFZ-induced renal toxicity in rats. The first group of rats was a normal control (CNT); the second group received CFZ (4 mg/kg b.w.); the third and fourth groups received TQ (10 and 20 mg/kg b.w.) 2 h before receiving CFZ; the fifth group received only TQ (20 mg/kg b.w.). This experiment was conducted for 16 days, and at the end of the experiment, blood samples and kidney tissue were collected for biochemical assays. The results indicated that administration of CFZ significantly enhanced serum marker levels such as BUN, creatinine, and uric acid in the CFZ group. Similarly, it was also noticed that CFZ administration induced oxidative stress by reducing antioxidants (GSH) and antioxidant enzymes (CAT and SOD) and increasing lipid peroxidation. CFZ treatment also enhanced the expression of IL-1ß, IL-6, and TNF-α production. Moreover, CFZ increased caspase-3 concentrations and reduced Nrf2 expression in the CFZ-administered group. However, treatment with 10 and 20 mg/kg TQ significantly decreased serum markers and increased antioxidant enzymes. TQ treatment considerably reduced IL-1ß, IL-6, TNF-α, and caspase-3 concentrations. Overall, this biochemical estimation was also supported by histopathological outcomes. This study revealed that TQ administration significantly mitigated the negative effects of CFZ treatment on Nrf2 expression. Thus, it indicates that TQ may have utility as a potential drug to prevent CFZ-induced nephrotoxicity in the future.

Capsaicin Ameliorates the Cyclophosphamide-Induced Cardiotoxicity by Inhibiting Free Radicals Generation, Inflammatory Cytokines, and Apoptotic Pathway in Rats.

Cyclophosphamide is an antineoplastic agent that has a broad range of therapeutic applications; however, it has numerous side effects, including cardiotoxicity. Furthermore, chili peppers contain a substance called capsaicin, having antioxidant and anti-inflammatory effects. Thus, this research paper focuses on the potential mechanism of capsaicin's cardioprotective activity against cyclophosphamide-induced cardiotoxicity by measuring the expression of oxidative and inflammatory marker such as interleukins and caspases. The following groups of rats were randomly assigned: only vehicle given for 6 days (control group); cyclophosphamide 200 mg/kg intraperitoneal on 4th day only (positive control group); capsaicin 10 mg/kg orally given for 6 days followed by cyclophosphamide 200 mg/kg on 4th day of treatment; capsaicin 20 mg/kg orally for six days followed by cyclophosphamide 200 mg/kg on 4th day of treatment; and maximum amount of capsaicin alone (20 mg/kg) orally for six days. Using ELISA kits, it was found that the cyclophosphamide administration significantly increased the levels of lactate dehydrogenase, troponin-I (cardiac cell damage marker), lipid peroxidation, triglyceride, interleukin-6, tumor necrosis factor-alpha, and caspase 3. However, it markedly reduced the antioxidant enzymes catalase and glutathione levels. Both doses of capsaicin could reverse cardiac cell damage markers, as shown by a significant decline in (lactate dehydrogenase and troponin-I). In addition, capsaicin significantly reduced the cytokine levels (interleukin-6 and tumor necrosis factor-alpha), caspase 3, lipid peroxidation, and triglycerides. However, capsaicin treatment significantly raised the antioxidant content of enzymes such as glutathione and catalase. The capsaicin-treated group restored the oxidative parameter's imbalance and generated considerable protection against cardiomyocyte harm from cyclophosphamide in male Wistar rats. These protective effects might be beneficial against the negative impacts of cyclophosphamide when used to treat cancer and immune-mediated diseases.