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Effects of fish oil on methotrexate-induced reproductive damage in rats
Volkan Ipek1, Kursat Kaya2, Cigdem Cebi3
1Faculty of Veterinary Medicine, Department of Pathology, Burdur Mehmet Akif Ersoy University, Burdur, Turkey.
Abstract:
Methotrexate (MTX) is a folic acid antagonist that is commonly used in paediatric and adult oncology to treat a variety of malignancies. Internal organs, including the testis, are severely cytotoxic and genotoxic to MTX. Omega-3, as an antioxidant, has been shown to protect rat testis tissue from injury. The effect of fish oil (FO) on MTX-induced reproductive damage in rats was investigated in this work. The 28 animals were divided into four groups for this purpose (control, FO, MTX, and MTX-FO). On the third day, the MTX group received a single intraperitoneal injection of 20 mg/kg MTX. Furthermore, in the FO and MTX-FO groups, FO was delivered through gavage once daily for 14 days. All animals euthanized under general anaesthesia on the 15th day. TBARS, catalase, glutathione peroxidase, glutathione (GSH), superoxide dismutase levels were measured biochemically. The Cosentino grading system was utilized for histology. Germ cell thickness and caspase-3 activity were also evaluated. In addition, sperm motility rate, epididymal sperm count, aberrant sperm rate, and sperm vitality were measured to assess sperm quality. Some TBARS levels have increased, but GSH levels decreased significantly in the MTX group. FO reduced TBARS levels while considerably increasing GSH levels. All sperm quality measures were significantly lowered in the MTX group, while FO had a recovery effect. There were no notable variations in histopathology across groups except for germ cell thickness, which reduced considerably in the MTX group and recovered with FO treatment. As a result, FO has been shown to reduce testicular toxicity following MTX treatment in rats.
Insights
Fish oil (FO) protects against methotrexate (MTX)-induced testicular damage in rats by reducing oxidative stress and improving sperm quality. This antioxidant effect helps mitigate the cytotoxic and genotoxic impacts of MTX on reproductive health.
Area of Science:
- Reproductive toxicology
- Oncology supportive care
- Nutritional biochemistry
Background:
- Methotrexate (MTX), a folic acid antagonist, is a cornerstone in cancer chemotherapy but exhibits significant testicular toxicity.
- Oxidative stress plays a crucial role in MTX-induced reproductive damage.
- Omega-3 fatty acids, found in fish oil (FO), possess antioxidant properties that may counteract cellular injury.
Purpose of the Study:
- To investigate the protective effects of fish oil (FO) against methotrexate (MTX)-induced testicular damage in a rat model.
- To evaluate the impact of FO supplementation on biochemical markers of oxidative stress and sperm quality parameters following MTX administration.
Main Methods:
- Adult male rats were divided into four groups: control, FO, MTX, and MTX-FO.
- MTX was administered intraperitoneally, while FO was given daily via gavage for 14 days.
- Biochemical assays (TBARS, antioxidant enzymes), histopathology, germ cell thickness, caspase-3 activity, and sperm quality parameters were assessed.
Main Results:
- MTX treatment significantly increased TBARS levels and decreased glutathione (GSH) levels, indicating oxidative stress and reduced antioxidant capacity.
- FO supplementation reversed these changes, lowering TBARS and increasing GSH levels.
- Sperm quality parameters (motility, count, morphology, vitality) were significantly impaired by MTX but improved with FO co-administration.
- Germ cell thickness was reduced by MTX and restored by FO treatment.
Conclusions:
- Fish oil (FO) demonstrates significant protective effects against methotrexate (MTX)-induced testicular toxicity in rats.
- FO mitigates MTX-induced oxidative stress and improves sperm quality, suggesting its potential as a supportive therapy in cancer patients undergoing MTX treatment.
