Astaxanthin Supplementation and Antioxidant Modulation in Methamphetamine Dependence: A Potential SIRT1/PGC-1α Pathway Mechanism.

Abstract

Background: Methamphetamine (METH) addiction remains a significant global health challenge, characterized by profound neurotoxicity and cognitive impairment. Emerging evidence suggests that the pathophysiology of METH dependence is closely linked to oxidative stress, where an imbalance between reactive oxygen species (ROS) production and antioxidant defense mechanisms leads to neuronal damage.
Aim: to evaluate the impact of Astaxanthin supplementation on antioxidant levels in methamphetamine-dependent patients, while investigating the mediating role of the SIRT1/PGC-1α pathway.
Method: A total of ninety men, aged between 18 and 45 years, The study design is as follows Group 1: Healthy individuals, non-drug users (control group),Group 2: Drug users who had been using methamphetamine for one year and Group 3: Drug users who had been using methamphetamine for one year and were administered astaxanthin treatment at a dose of 12 mg/day for thirty days.
Result: methamphetamine exposure induced significant oxidative damage and suppressed key neuroprotective markers. Specifically, MDA levels were markedly elevated in the untreated group (5.97 \pm 1.98) compared to controls (2.07 \pm 0.60), while Astaxanthin treatment significantly reduced these levels to 4.38 \pm 1.28 (p < 0.001). Similarly, the compensatory increase in Catalase activity observed in the untreated group (56.07 \pm 16.24) was partially normalized following treatment (46.00 \pm 13.48). At the molecular level, methamphetamine exposure caused a substantial decline in PGC-1$\alpha$ and SIRT1 levels; however, Astaxanthin supplementation facilitated a significant partial recovery of both biomarkers (0.76 \pm 0.40 and 0.81 \pm 0.46, respectively). Overall, these findings demonstrate that Astaxanthin effectively mitigates oxidative stress and modulates the SIRT1/PGC-1$\alpha$ pathway, although levels did not return to baseline control values.
Conclusion: Astaxanthin (AST) acts as a potent neuroprotective agent in the context of methamphetamine (METH) dependence by modulating the SIRT1/PGC-1α signaling pathway.