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Thymoquinone Ameliorates Carfilzomib-Induced Renal Impairment by Modulating Oxidative Stress Markers,
Marwa M Qadri1,2, Mohammad Firoz Alam1, Zenat A Khired3
1Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia.
Abstract:
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-1β, 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-1β, 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.
Insights
Thymoquinone (TQ) effectively protected against carfilzomib (CFZ)-induced kidney damage in rats by reducing oxidative stress and inflammation. This study highlights TQ as a potential therapeutic agent for preventing chemotherapy-related nephrotoxicity.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Chemotherapy-induced kidney damage is a significant challenge in cancer treatment.
- Carfilzomib (CFZ), a proteasome inhibitor used for multiple myeloma, is associated with severe nephrotoxicity.
- There is an unmet need for effective nephroprotective and antioxidant therapies against CFZ-induced renal injury.
Purpose of the Study:
- To investigate the protective effects of thymoquinone (TQ) against carfilzomib (CFZ)-induced nephrotoxicity in a rat model.
- To evaluate the antioxidant and anti-inflammatory potential of TQ in mitigating CFZ-induced renal damage.
Main Methods:
- Rats were divided into groups receiving normal control, CFZ alone, TQ (10 and 20 mg/kg) followed by CFZ, or TQ alone.
- Biochemical markers of kidney function (BUN, creatinine, uric acid), oxidative stress (GSH, CAT, SOD, lipid peroxidation), and inflammation (IL-1β, IL-6, TNF-α) were assessed.
- Caspase-3 expression and Nrf2 levels were measured, alongside histopathological examination of kidney tissues.
Main Results:
- CFZ administration significantly elevated serum markers of kidney damage and induced oxidative stress and inflammation.
- CFZ treatment decreased antioxidant levels and Nrf2 expression while increasing lipid peroxidation and caspase-3.
- TQ treatment (10 and 20 mg/kg) significantly reversed these effects, reducing kidney damage markers, oxidative stress, and inflammation, and preserving Nrf2 expression.
Conclusions:
- Thymoquinone (TQ) demonstrates significant nephroprotective effects against carfilzomib (CFZ)-induced renal toxicity in rats.
- TQ mitigates CFZ-induced nephrotoxicity by enhancing antioxidant defense, reducing oxidative stress, suppressing inflammation, and modulating Nrf2 expression.
- TQ shows promise as a potential therapeutic agent for preventing carfilzomib-induced nephrotoxicity.
