The augment effects of magnesium hydride on the lipid lowering effect of atorvastatin: an in vivo and in vitro investigation

Abstract

There is strong evidence connecting increased serum lipid levels to cardiovascular disorders, including atherosclerosis. Statins is prescribed as the primary medication to decrease lipid levels. Recent research has demonstrated that hydrogen possesses anti-inflammatory and antioxidant properties by modulating the expression of peroxisome proliferator-activated receptor gamma coactivator-1α, ultimately leading to the preservation of lipid homeostasis. Magnesium hydride (MgH2) is a prolonged stable hydrogen storage medium, which can be utilized to investigate its synergistic lipid-lowering effect with statins and its detailed molecular mechanism, both in vivo and in vitro. To ascertain the safety and efficacy of MgH2, we executed a comprehensive research of its influence on both physiological and pathological metrics. We noted a substantial diminution in lipid levels when MgH2 was integrated with atorvastatin, as attested by oil red staining. Furthermore, we scrutinized the regulatory effect of MgH2 on cytochrome P450 3A, which is a metabolic enzyme of statins, and discovered that it could be reduced by the MgH2. Concluding from our results, we propose that MgH2 inhibits the expression of cytochrome P450 3A in the liver and exerts an auxiliary lipid-lowering effect by increasing the blood concentration of statins. By augmenting our comprehension of MgH2’s role in ameliorating lipid metabolism, we aspire to develop more promising therapies in the future.

Study details

Article type

Original Research

Disease / injury model

High-fat diet-induced hyperlipidemia (mouse model), palmitic acid-induced steatosis (cell model)

Duration

16 weeks

Dose comparison

Different concentrations of MgH2 (0–1000 μM in vitro, 0.5 g/kg in vivo) and atorvastatin (5 mg/kg in vivo, 20 nM in vitro) were compared for their effects on lipid metabolism and cell viability.

Dose-dependent effect

Yes

Outcome

Positive

Findings

Magnesium hydride (MgH2) significantly enhances the lipid-lowering effect of atorvastatin in both in vivo (mouse) and in vitro (AML-12 cell) models, primarily by inhibiting hepatic CYP3A expression, thereby increasing statin blood concentration and reducing lipid accumulation. MgH2 alone is safe and does not adversely affect liver or kidney function.