Alpha-linolenic acid is one of the fatty acids known as omega 3. Previous studies have shown the antioxidant and anti-inflammatory effects of alpha-linolenic acid, which prevented cell damage by inhibiting apoptotic pathway. Also, it is known that gentamicin activates apoptotic mediators and causes necrosis in the kidney. Due to this reason, we planned a study to evaluate the protective effects of alpha-linolenic acid on gentamicin induced ototoxicity by evaluating inflammation and apoptotic mediators. For this purpose, 100 mg/kg gentamicin (i.p; intraperitoneally) and 200 mg/kg alpha-linolenic acid (gavage) are administered to mice for 9 days. On 9th and 10th days, rotarod performance was assessed to test the effect of gentamicin and alpha-linolenic acid treatment on the motor coordination of mice. Gentamicin treatment decreased fall latency of mice and gentamicin treatment together with alpha-linolenic acid increased fall latency of mice. Gentamicin treatment also increased expression of phospholipase A2(plA2), cyclooxygenase-2(COX-2) and inducible nitric oxide syntheses (iNOS). Furthermore, it increased Bax and caspase-3, which are proapoptotic proteins and decreased bcl-2 that is an antiapoptotic protein. Gentamicin treatment together alpha-linolenic acid recovered the change of expression of these enzymes. In conclusion, this study showed that alpha-linolenic acid will be useful to prevent gentamicin-induced ototoxicity by inhibiting apoptosis and inflammation.

This study aimed to reveal the possible protective effect of dapagliflozin (DAPA) against acute kidney damage due to cyclosporine A (CsA). Thirty-two mice with an eight-week-old Balb\c albino strain were divided into four groups: control group, CsA group, DAPA group, and CsA + DAPA group. On day 9 of treatment, the animals were decapitated, and bilateral nephrectomy was performed. Oxidative stress and apoptosis were evaluated with caspase-3 activity, total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde (MDA), myeloperoxidase (MPO), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the right kidney resection material. The left kidney resection material was evaluated histopathologically. CsA increased caspase-3 activity, Bax, TOS, MDA, TAS, and MPO levels, and the administration of DAPA with CsA significantly reduced this increase in levels (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p < 0.001, respectively). CsA decreased Bcl-2 levels, and administration of CsA + DAPA significantly increased Bcl-2 levels compared with only CsA administration (p < 0.001). Additionally, administration of DAPA significantly reduced the histopathological findings (parenchymal inflammation, hyaline cast formation, vacuolization, and lysis of renal tubular cells) caused by CsA. DAPA reduces oxidative stress, apoptosis, and histopathological damage caused by CsA in renal tissue.

Breast cancer holds the top position among the cancers occurring in women. Despite the utilization of surgical removal, chemotherapy, and radiation therapy, there is currently no conclusive treatment available to prevent breast cancer. New treatment approaches are being studied since traditional chemotherapeutics also damage healthy cells. Tempol (TPL) is a potent antioxidant agent that has been shown to exhibit anticancer activity. The objective of this research was to examine the impacts on cell proliferation and apoptosis by using methotrexate (MTX) and TPL individually and in combination on MCF7 breast cancer cells. MCF7 cells were exposed to TPL, MTX, and MTX + TPL for 48 h. The effects of the administered drugs on cell viability were determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assay analysis was conducted to assess the levels of the antiapoptotic protein Bcl-2, the pro-apoptotic protein Bax, and the activity of caspase-3 in MCF7 cells. Increasing concentrations of TPL and MTX significantly decreased the proliferation in MCF7 cells in both solo and combined use. Solo and combined use of TPL and MTX significantly increased caspase-3 activity and Bax levels and significantly decreased Bcl-2 levels in the cells. This study revealed that the solo use of TPL and MTX inhibited proliferation and increased apoptotic activity in the cells. In addition, TPL increased the antiproliferative and apoptosis efficiency of MTX on cancer cells as a result of the combined use of these drugs.

Purpose: Osteotoxicity, a common consequence of Methotrexate (MTX) therapy, significantly compromises bone health by inducing oxidative stress and disrupting bone remodeling. This study examines the protective effects of Tempol, a nitroxide compound with antioxidant properties, against MTX-induced osteotoxicity. Methods: Osteocyte-like MLO-Y4 cells were cultured and treated with Tempol and MTX to evaluate changes in apoptotic mediators, MAPK signaling pathways, and oxidative stress parameters. Results: MTX treatment significantly increased caspase-3 activity and Bax expression while decreasing Bcl-2 levels, thereby creating a pro-apoptotic environment. It also activated stress-related pathways by elevating JNK and ERK activities. Conversely, Tempol effectively countered these effects by restoring the balance of apoptotic mediators, downregulating MAPK activation, and enhancing Total Antioxidant Status (TAS). Additionally, Tempol reduced Total Oxidant Status (TOS) and improved the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Conclusion: These findings highlight Tempol’s potential to mitigate oxidative stress and apoptosis linked to MTX therapy, supporting its use as an adjunctive treatment to protect bone health in patients undergoing MTX therapy. Emphasizing Tempol’s clinical implications as a protective agent reinforces the urgency for further research into its long-term effects on cellular viability and bone integrity in the context of chemotherapy.