The Investigation of the Antitumor Agent Toxicity and Capsaicin Effect on the Electron Transport Chain Enzymes, Catalase Activities and Lipid Peroxidation Levels in Lung, Heart and Brain Tissues of Rats

Abstract

Cisplatin is one of the most active cytotoxic agents in cancer treatment. To clarify the interaction with mitochondria, we hypothesize that the activities of mitochondrial electron transport chain (ETC) enzymes succinate dehydrogenase (SDH) and cytochrome c oxidase (COX), nucleotide levels, as well as levels of catalase (CAT) enzyme and membrane lipid peroxidation (LPO) can be affected by cisplatin. There was a significant decrease of both SDH and COX activities in the lung, heart, and brain tissues at the 1st day after cisplatin exposure, and the observed decreased levels of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) in comparison with the control could be because of cisplatin-induced mitochondrial dysfunction. The investigations suggested that cisplatin inhibits SDH, COX, and ATP synthase. The higher LPO level in the studied tissues after 1 and 4 days post-exposure to cisplatin compared to control can be inferred to be a result of elevated electron leakage from the ETC, and reactive oxygen species (ROS) can lead to wide-ranging tissue damage such as membrane lipid damage. Consequently, it was observed that capsaicin may have a possible protective effect on ETC impairment caused by cisplatin. The activities of SDH and COX were higher in heart and brain exposed to cisplatin + capsaicin compared to cisplatin groups, while LPO levels were lower. The investigated results in the cisplatin + capsaicin groups suggested that the antioxidant capacity of capsaicin scavenges ROS and prevents membrane destruction.

Panax�notoginseng Saponins protect auditory cells against cisplatin‑induced ototoxicity by inducing the AKT/Nrf2 signaling‑mediated redox pathway

“…Hoechst 33258 and PI double staining. a total of 1x10 5 Hei-oc1 cells were diluted in 4 ml complete medium and incubated in 6-well plates with 100 µg/ml PnS for 2 h prior to treatment with cisplatin (20 µM) at 33˚C in a humidified 10% co 2 environment for 24 h. Following two washes with PBS, the cells were fixed with 4% paraformaldehyde for 30 min at 4˚C, and stained with 2 µg/ml Hoechst 33258 and 1 µg/ml Pi for 20 min in the dark at 4˚C. Finally, following two washes with PBS, the cells were visualized using a Leica DMi8 fluorescence microscope (magnification, x200; Leica Microsystems, Inc.).…”

“…To assess the dna fragmentation using TUNEL, cells were fixed with 1% formaldehyde for 10 min at room temperature. Following incubated with 100 µg/ml PnS for 2 h prior to treatment with cisplatin (20 µM) at 33˚C in a humidified 10% CO 2 environment for 24 h, a total of 1x10 5 Hei-oc1 cells were incubated with 20 µg/ml proteinase K for 60 min at room temperature. The slides were then rinsed with PBS for 3 min, dried and incubated in 20 µl Tunel reaction mixture for 1 h at room temperature.…”

“…Determination of intracellular ROS. a total of 1x10 5 Hei-oc1 cells were diluted in 4 ml complete medium and cultured in 6-well plates. The cells were pre-incubated with 100 µg/ml PNS for 2 h prior to incubation with cisplatin (20 µM) at 33˚C in a humidified 10% CO 2 environment for 24 h. Subsequently, the cells were washed with cold PBS twice and incubated with 2',7'-dichlorofluorescein diacetate (dcFH-da; invitrogen; Thermo Fisher Scientific, Inc.) for 20 min at room temperature.…”

“…cisplatin is a typical chemotherapeutic drug that is widely used in the treatment of a variety of solid tumors (1,2). However, the dose-limiting side effects of high concentrations of cisplatin, such as renal damage, neurotoxicity and ototoxicity can restrict its clinical application (3)(4)(5). among patients that receive cisplatin chemotherapy, >90% may end up with ear-associated adverse effects (3,6).…”

“…among patients that receive cisplatin chemotherapy, >90% may end up with ear-associated adverse effects (3,6). However, currently no effective treatment exists to avoid or reduce ototoxicity induced by cisplatin (5,(7)(8)(9). Therefore, the prevention of ototoxicity induced by cisplatin has become a major focus in tumor therapy.…”