Histomorphological changes in the pancreas and kidney and histopathological changes in the liver in male Wistar rats on antiretroviral therapy and melatonin treatment.

Combination antiretroviral therapy (cART) has shown to cause inflammation, cellular injury and oxidative stress, whereas melatonin has been successful in reducing these effects. The aim of the study was to determine potential morphometric changes caused by cART in combination with melatonin supplementation in human immunodeficiency virus (HIV)-free rats. Tissue samples (N = 40) of the pancreas, liver and kidney from a control (C/ART-/M-), cART group (C/ART + ), melatonin (C/M + ) and experimental group (ART+/M + ) were collected and stained with haematoxylin and eosin (H&E) and evaluated for histopathology. The pancreata were labelled with anti-insulin and anti-glucagon to determine α- and ß-cell regions. Kidneys were stained with periodic acid Schiff (PAS) to measure the area, perimeter, diameter and radius of renal corpuscles, glomeruli and proximal convoluted tubules (PCTs). Blood tests were conducted to determine hepatotoxicity. No significant changes in histopathology were seen. Melatonin stimulated pancreatic islet abundance, as the number of islets per mm2 was significantly higher in the C/M+ than in the C/ART-/M- and ART+/M+. Parameters of the renal corpuscle, glomeruli, renal space and PCTs were significantly lower in the C/ART+ compared to the other groups, thus cART may have caused tubular dysfunction or cellular damage. A significant increase in serum haemoglobin was observed in the C/ART+ compared to the C/ART-, which showed cART increases serum haemoglobin in the absence of immune deficiency. Serum lipids were significantly decreased in the C/M+ compared to the C/ART-, possibly due to the effect of melatonin on the decrease of lipolysis, decreasing effect on cholesterol absorption and stimulation of lipoprotein lipase (LPL) activity. In conclusion, we have demonstrated that melatonin stimulated α-cell production, increased the number of pancreatic islets and caused a decrease in total lipids, whereas cART increased serum haemoglobin and decreased various parameters of the nephron in an HIV-free rat model, suggestive of tubular dysfunction.

Mucin secreting cells in the stomach and colon are altered by combination antiretroviral treatment in an obese rat model.

Mucins, secreted by intestinal goblet cells, form an integral part of the intestinal biofilm, which is important for the functioning of a healthy gastrointestinal tract (GIT). This mucous layer is sensitive to factors such as diet, drugs and inflammation. Histochemically, mucins can be classified as neutral or acidic, where acidic mucins can contain sulphate groups (sulphomucins) or sialic acid (sialomucins). The aim of the present study was to determine the composition of various mucin secreting cells using histochemical stains in rats fed on a high calorie diet (HCD) treated with antiretroviral therapy (ART). Wistar rats (N=24) were divided into a lean control group (C/ART-), high calorie diet group (C/HCD+), ART group (C/ART+) and HCD and ART group (HCD+/ART+). The body of the stomach as well as the colon were stained with Alcian Blue Periodic Schiff (ABPAS) to distinguish between neutral and acidic mucins and Alcian Blue Aldehyde Fuschin (ABAF) to distinguish between sialo-and sulphomucins. An increase of the total gastric mucous cells was observed in the HCD+/ART+ group compared to the C/ART- group using both ABPAS and ABAF. A decrease of neutral cells in the distal part of the colonic crypts in the C/HCD+ and C/ART+ groups compared to the C/ART- group were observed. Mixed goblet cells in the colonic crypts of the C/ART- and HCD+/ART+ groups were decreased in comparison to the C/ART+ group. The study showed that the total mean percentage of mucous cells in the stomach as well as the total amount of neutral goblet cells in the colon were most affected by ART and a HCD. These changes in a rat model suggest that the quality of the biofilm may be altered and should be considered when ART is prescribed to obese patients.