Abstract
Background:
Magnesium is widely used for its physiological and therapeutic benefits and is generally regarded as a hepatoprotective agent in deficient states. However, the effects of varying durations of magnesium supplementation on hepatobiliary and intestinal function remain incompletely characterized.

Aim:
This study investigated and compared the effects of short- and long-term oral magnesium administration on liver function indices, bile secretion, intestinal fluid dynamics, and glucose absorption in an experimental animal model.

Methods:
Experimental animals were allocated into short-term and long-term magnesium-treated groups and their respective controls (n = 10 per group). Magnesium-treated animals received 22.84 mg/kg magnesium, whereas controls received an equivalent volume of normal saline. Short-term treatment lasted 1 month, and long-term treatment lasted 2 months. Following each treatment phase, the animals were sacrificed under isoflurane anesthesia. Serum liver enzymes (ALT, AST, and ALP), total and conjugated bilirubin, biliary cholesterol, bile secretion rate, electrolyte composition, serosal and mucosal fluid transfer, gut fluid uptake, and intestinal glucose absorption were measured. The liver histology was also evaluated. Data were analyzed using appropriate parametric or non-parametric tests after assessing the distributional assumptions. Results were expressed as mean ± SD, with adjustment for multiple comparisons where applicable, and statistical significance was set at adjusted p < 0.05.

Results:
Short-term magnesium administration was associated with increased bile secretion, elevated biliary sodium, potassium, and chloride concentrations, and enhanced intestinal glucose uptake, while bicarbonate levels showed a transient reduction. In contrast, long-term administration was associated with reduced bile flow, altered biliary electrolyte composition, elevated liver enzyme activities and bilirubin levels, and impaired intestinal glucose absorption. Histological examination revealed hepatocellular alterations, inflammatory changes, and vascular disturbances in the long-term group. Serosal and mucosal fluid transfer and gut fluid uptake did not differ significantly between the groups.

Conclusion:
Although the study was limited by the modest sample size, the absence of serum magnesium measurements, the lack of oxidative stress and inflammatory biomarker assessment, and the reliance on biochemical indices without detailed mechanistic validation, oral magnesium administration produced duration-dependent alterations in hepatobiliary and intestinal parameters under the conditions of this study. Short-term exposure appeared to enhance bile secretion and glucose uptake, whereas long-term administration was associated with biochemical and histological changes suggestive of hepatic stress. Given the inconsistencies with the broader clinical literature and the absence of mechanistic confirmation, these findings should be interpreted cautiously. Further well-powered studies incorporating mechanistic biomarkers and exposure verification are required to establish clinical implications.

Key words: Absorption; Bile secretion; Liver enzymes; Magnesium.