Effect of chlorpyrifos and its metabolites on skeletal system development of chick embryo.

RESEARCH FOCUS: Chlorpyrifos is an organophosphate insecticide used primarily to control pests on a variety of food and feed crops. Humans are directly or indirectly exposed to this pesticide through food, air, and occupation. The ill effects of chlorpyrifos on various organ systems of human has been widely documented, but less is known about its influence on human bones. AIM: To analyze the effect of chlorpyrifos and its metabolites 3,5,6-trichloro-2-pyridinol (TCPy) on the skeletal system of the chick embryo. MATERIALS AND METHODS: Fertilized chick eggs were exposed to different concentrations of chlorpyrifos and its metabolite 3,5,6-TCPy on 1.5 days of incubation. The proximal phalanx of 18-day-old embryos was analyzed for defects in growth and ossification through histopathology, immunohistochemistry, angiogenesis assay, and gene expression study. RESULTS: Dose-dependent variations in developing bone of chick embryo were observed. Histochemical and histomorphometry studies of proximal phalanx showed increased in the growth plate length (F(9, 59) = 228.9509, p = .00001) with a reduction in the total length of the phalanx (F(9, 59) = 109.9905, p = .00001), decreased mineralization (F(9, 59) = 224.6872, p = .00001), decreased blood islands in the bone marrow (F(9, 59) = 7.7083, p = .0001) of chlorpyrifos, and 3,5,6-TCPy-exposed group. Significant downregulations in the expression patterns of the transcription factors, such as SOX9, RUNX2, and ALP, were also observed. CONCLUSION: Chlorpyrifos and its metabolite 3,5,6-TCPy exposure alters the chondrogenesis in the growth plate cartilage of long bone in chick embryo. The pesticide and its metabolite also interfere in ossification.

Naringin (4',5,7-Trihydroxyflavanone 7-Rhamnoglucoside) Attenuates ß-Cell Dysfunction in Diabetic Rats through Upregulation of PDX-1.

BACKGROUND: Pancreatic duodenal homeobox-1 (PDX-1) is a key transcription factor which regulates Insulin gene expression and insulin secretion in adult ß-cells and helps to maintain ß-cells mass. Naringin, a flavanone, owing to its anti-oxidant property, is reported to have antidiabetic effects. OBJECTIVES: The present study tries to evaluate the role of naringin on the ß-cell-specific transcription factor PDX-1 in diabetic rats. METHODS: Diabetes was induced in male rats using streptozotocin and treated with naringin (100 mg/kg) orally for 4 and 8 weeks. Serum insulin level, Pdx-1 and Insulin gene expression, and PDX-1 protein expression were assessed in the rat pancreas. Histopathological and ultrastructural changes in the islet and ß-cells were observed. RESULTS: Naringin prevented leukocytic infiltration in the pancreas of diabetic rats and recouped the ß-cells with adequate secretory granules. Naringin-treated diabetic rats showed significantly increased mRNA expression of Pdx-1 and Insulin genes, increased expression of transcription factor PDX-1, and higher serum insulin levels than the diabetic control animals. These changes were more pronounced in the 8-week naringin-treated diabetic animals. CONCLUSIONS: Naringin was found to be an effective antidiabetic agent which increased Insulin gene expression and insulin secretion by upregulating the PDX-1 gene and protein expression.

Naringin Ameliorates Streptozotocin-Induced Diabetes through Forkhead Box M1-Mediated Beta Cell Proliferation.

BACKGROUND: Adult pancreatic beta cells, though quiescent, can proliferate in response to physiological need. This inherent character is used in exploring the possibilities of expanding the beta cell mass in the treatment of diabetes. Forkhead box M1 (FoxM1) transcription factor is an important regulator in the proliferation and survival of adult beta cell mass. Naringin, a flavanone glycoside, is reported to have antidiabetic activity and exhibited an increase in insulin levels in diabetic animals. OBJECTIVES: The present study tried to evaluate the role of naringin in the regulation of FoxM1 in the pancreas of diabetic rats and to reascertain its antilipidemic and antioxidant properties. METHODS: Diabetes was induced in male rats using streptozotocin and treated with naringin (100 mg/kg) orally for 4 and 8 weeks. Serum biochemical parameters, insulin, gene and protein expression of FoxM1, and antioxidant markers in rat pancreas were analyzed. RESULTS: Naringin administration reduced the blood sugar, urea, creatinine, and cholesterol values and improved the pancreatic antioxidant status in diabetic rats. Naringin-treated diabetic rats showed a significant increase in mRNA and protein expression of FoxM1 compared to the diabetic control rats, indicating regeneration of cells. It also increased the insulin immunopositive cells, indicating functional beta cells. CONCLUSION: Naringin was found to upregulate the FoxM1 transcription factor in diabetic animals, which influenced the proliferation and functional status of beta cells.