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.