Influence of dietary protein deficiency on the progression and resolution of CCl₄-induced liver damage

Malnutrition remains a major global health challenge and is associated with increased susceptibility to liver disease and impaired recovery following hepatic injury. This research assesses the impact of a low-protein diet (LPD) on mice subjected to carbon tetrachloride (CCl₄)-induced liver damage. How an established state of protein deficiency affects the temporal progression of liver injury and the subsequent process of hepatic recovery remains poorly understood. Therefore, this study investigated the influence of long-term dietary protein-deficiency on the progression and resolution of CCl₄-induced liver injury using a longitudinal experimental approach. A preliminary dose-selection study identified 2 mL/kg CCl₄ as the optimal dose in both dietary groups-normal diet (ND) and LPD. The time course of injury due to CCl₄ post-administration was assessed at 0-72 h. Injury was apparent by 1 h, reached a maximum at 24 h, and was more significant in the LPD group compared to the ND group. By 72 h, ND mice showed near-complete recovery, whereas liver injury persisted in LPD mice. Inflammatory markers (TNF-α and IL-6) indicated greater inflammatory responses in the LPD mice. Also, elevated PCNA and MDA levels in the LPD mice suggest that there was increased oxidative stress in addition to an increased compensatory cell proliferation response. Histopathological assessment revealed more extensive tissue damage, including necrosis, apoptosis, and delayed regenerative recovery, in LPD mice. Therefore, by defining the temporal pattern of liver injury and recovery, this study provides a framework for identifying optimal intervention windows and evaluating therapeutic strategies under protein-deficiency conditions.