Histological and immunohistochemical effects of Curcuma longa on activation of rat hepatic stellate cells after cadmium induced hepatotoxicity

Abstract

The liver is a target for toxic chemicals such as cadmium (Cd). When the liver is damaged, hepatic stellate cells (HSC) are activated and transformed into myofibroblast-like cells, which are responsible for liver fibrosis. Curcuma longa has been reported to exert a hepato-protective effect under various pathological conditions. We investigated the effects of C. longa administration on HSC activation in response to Cd induced hepatotoxicity. Forty adult male albino rats were divided into: group 1 (control), group 2 (Cd treated), group 3 (C. longa treated) and group 4 (Cd and C. longa treated). After 6 weeks, liver specimens were prepared for light and electron microscopy examination of histological changes and immunohistochemical localization of alpha smooth muscle actin (αSMA) as a specific marker for activated HSC. Activated HSC with a positive αSMA immune reaction were not detected in groups 1 and 3. Large numbers of activated HSC with αSMA immune reactions were observed in group 2 in addition to Cd induced hepatotoxic changes including excess collagen deposition in thickened portal triads, interlobular septa with hepatic lobulation, inflammatory cell infiltration, a significant increase in Kupffer cells and degenerated hepatocytes. In group 4, we observed a significant decrease in HSC that expressed αSMA with amelioration of the hepatotoxic changes. C. longa administration decreased HSC activation and ameliorated hepatotoxic changes caused by Cd in adult rats.

Pancreas–Liver–Adipose Axis: Target of Environmental Cadmium Exposure Linked to Metabolic Diseases

“…In acute Cd exposure, the liver takes up and stores a significant quantity of metal. Cd-hepatotoxicity during the initial hours after exposure produces ischemia, Kupffer cell activation, and neutrophil infiltration [ 133 ]. Liver histopathological hallmarks after acute Cd exposure are cytoplasmic vacuolization, necrosis, congested blood vessels, mitophagy, fatty droplets, glycogen depletion, and portal fibrosis [ 134 ].…”

“…Cadmium hepatotoxicity is closely related to inflammation. Previous studies have demonstrated that Cd-activated Kupffer cells release a number of inflammatory mediators, such as TNF-α, IL-1β, IL-6, and IL-8, which initiate a cascade of cellular responses, leading to liver damage [ 133 , 135 ]. Hepatotoxicity is reduced when Kupffer cells are selectively inhibited or suppressed [ 134 , 136 ].…”