Abstract
Orlistat is a safe and effective drug to treat obesity by acting as a pancreatic and gastric lipase inhibitor, resulting in reduction in fat absorption. There is also concern that it may be linked with an increased threat of serious hepatic incidents. The present work was carried out to study the effect of orlistat on the histological, immunohistochemical and electron microscopic structure of the liver in the adult male albino rats and the possible protective role of β-carotene administration. Forty adult albino rats were subjected to experiment for two weeks as follows: group 1 (control), group II, each animal received 0.52 mg/kg bw/day β-Carotene, group III, each animal received orlistat 32 mg/kg/day, and group IV received β-Carotene, 1hour before the administration of orlistat at same dose of group II & III. The liver from each animal was dissected out and processed for histological, (light and electron microscopic study). The result of Hep-Par1 for immunohistochemistry was statistically analyzed. The results showed that orlistat treated group displayed variable disturbance of liver architecture, from dilatation, congested central and portal veins, branching of bile ductules, mononuclear cellular infiltration, areas of hemorrhages, cytoplasmic vacuolation and pyknotic nuclei. The most obvious changes were that degenerative changes in hepatocytes led to depletion of glycogen content of hepatocytes. Hep Par-1 revealed a wide area of negative immune expression around the central vein and in some hepatocytes. Other hepatocytes expressed weak reaction. Ultrastructure examination displayed hepatocytes with swollen mitochondria and others with an electron-dense matrix. The combined treatment of β-Carotene and orlistat led to a marked improvement in most of the previously mentioned changes. It was concluded that orlistat-induced hepatic toxicity. Thus, clinicians should cautiously monitor their patients for signs of hepatic dysfunction. Using an antioxidant such as β-Carotene decreased the toxicity of orlistat.
Highlights
Obesity has been involved in many chronic conditions, comprising cardiovascular disease, diabetes mellitus, hypertension, obstructive sleep apnoea, hyperlipidaemia, fatty liver disease and malignancy [1]
The results showed that orlistat treated group displayed variable disturbance of liver architecture, from dilatation, congested central and portal veins, branching of bile ductules, mononuclear cellular infiltration, areas of hemorrhages, cytoplasmic vacuolation and pyknotic nuclei
Immunohistochemical results for Hep Par-1 in the control liver section showed strong positive Hep Par-1 immunoreaction in the form of coarsely scattered granules throughout the hepatocytes cytoplasm with narrow negative immunoreaction around the central vein (Figure 3(A))
Summary
Obesity has been involved in many chronic conditions, comprising cardiovascular disease, diabetes mellitus, hypertension, obstructive sleep apnoea, hyperlipidaemia, fatty liver disease and malignancy [1]. Orlistat was official by the Food and Drug Administration (FDA) in 1998 for weight loss. Orlistat is the first gastrointestinal lipase inhibitor for the management of obesity [2]. Orlistat is a dominant inhibitor of gastrointestinal lipase. Orlistat deactivated gastrointestinal lipase, decreasing the absorption of dietary fat [5]. Orlistat diminished fat absorption by binding covalently to the serine residue of the active site of gastric and pancreatic lipases. It was suggested that orlistat administration with fat comprising foods partly prevented the hydrolysis of triglycerides, decreasing the consequent absorption of monoglycerides and free fatty acids [6]. Orlistat has been shown to decrease total cholesterol and low-density lipoprotein levels independent of weight loss [11].
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