Omega-3 fatty acids mitigate methamphetamine-induced pulmonary oxidative stress, antioxidant depletion, neutrophilic inflammation, caspase-3 apoptosis, and bioenergetic dysfunction in male Wistar rats.

BACKGROUND: Methamphetamine (METH) is a widely misused psychostimulant whose pulmonary toxicity is poorly characterised. Omega-3 fatty acids (Omega-3 FAs) are nutritional lipids with established antioxidant and anti-inflammatory properties, yet their capacity to protect against METH-induced lung injury has not been studied. OBJECTIVES: To investigate the effects of chronic METH exposure on pulmonary oxidative stress, antioxidant defences, inflammation, apoptosis, and energy metabolism, and to evaluate whether omega-3 FA supplementation attenuates selected markers of METH-induced pulmonary injury. METHODS: Twenty male Wistar rats were allocated to four groups (n = 5): Control, METH (10 mg/kg/day), Omega-3 (300 mg/kg/day EPA/DHA), and METH + Omega-3. All treatments were administered once daily by oral gavage for 60 consecutive days. Lung homogenates were analysed for pro-oxidant, antioxidant, inflammatory, apoptotic, and metabolic markers. Pulmonary histopathology was evaluated using H&E-stained sections. RESULTS: METH significantly increased MDA, H2O2, XO, uric acid, DFI, MPO, LDH, IL-1β, TNF-α, caspase-3, pyruvate, and lactate while reducing GPx, GSH, GST, total thiol, NO, and Ca2+-ATPase (all p < 0.05). Histopathology revealed pneumonitis with perivascular inflammatory infiltration in METH-only animals. Omega-3 co-supplementation significantly attenuated several injury markers, with statistically confirmed rescue of MPO, DFI, LDH, Ca2+-ATPase, lactate, and GPx. Attenuation of MDA, H2O2, IL-1beta, TNF-alpha, caspase-3, and uric acid was observed numerically but did not reach statistical significance versus METH alone. The pyruvate and lactate accumulation in METH animals, combined with Ca2+-ATPase suppression, indicates a shift toward anaerobic glycolysis consistent with mitochondrial respiratory dysfunction; omega-3 co-supplementation partially corrected this bioenergetic profile. The pyruvate and lactate accumulation in METH animals, combined with Ca2+-ATPase suppression, indicates a shift toward anaerobic glycolysis consistent with mitochondrial respiratory dysfunction; omega-3 co-supplementation partially corrected this bioenergetic profile. CONCLUSION: Omega-3 fatty acids attenuated METH-induced pulmonary oxidative stress, inflammation, apoptosis, and metabolic disruption in this preclinical model. These findings justify further dose-response and mechanistic studies before any clinical translation can be considered. CLINICAL TRIAL NUMBER: not applicable.