Amira Mahjoubi Samet

Hepatotoxicity induced by gibberellic acid in adult rats and their progeny.

Gibberellic acid (GA(3)), a plant growth regulator, was largely used in agriculture of many countries including Tunisia. However, its potential hazardous effects on human health were relatively unexplored. The purpose of this study was to investigate the effects of GA(3) on hepatic function in female rats and their pups. Animals were given daily 200 ppm GA(3) in drinking water from the 14th day of pregnancy until day 14 after delivery. It was found that GA(3) induced liver damages as evidenced by the elevation of plasma aminotransferases (ALT, AST), lactate dehydrogenase activities, bilirubin and albumin levels. Hepatotoxicity was objectified by the significant increase of malondialdehyde (MDA) level and a decrease of antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione content in liver of suckling pups and their mothers. Impairment of hepatic function corresponded histologically. We have observed blood vessels congestion and leucocytes infiltration, which were more pronounced in hepatocytes of dams than those of suckling pups. Results of this current study suggest that exposure rats to GA(3) induces hepatotoxicity and histopathological changes in liver of female rats and their progeny.

2,4-Dichlorophenoxyacetic acid effects on nephrotoxicity in rats during late pregnancy and early postnatal periods

2,4-Dichlorophenoxyacetic acid (2,4-D) is largely used as a selective herbicide in Tunisia. The purpose of this study was to investigate the effects of 2,4-D on the kidneys of adult rats and their suckling pups. Female Wistar rats were divided into two groups: the controls and the treated rats that received 600 mg/L of 2,4-D in their drinking water from the 14th day of pregnancy until day 14 after delivery. Exposure to 2,4-D induced nephrotoxicity as evidenced by an increase in thiobarbituric acid reactive substances and protein carbonyl levels and a decrease in antioxidant enzyme activities such as catalase, superoxide dismutase, glutathione peroxidase in the kidneys of suckling pups and their mothers. In addition, a significant decline in kidney glutathione, non-protein thiol and vitamin C levels was also observed. Histological changes, seen in the kidney of mothers and their pups treated with 2,4-D are characterized by a narrowed Bowmans space, tubular epithelial cells degeneration, widened tubular lumen and vascular congestion.

Oxidative stress induced by 2,4-phenoxyacetic acid in liver of female rats and their progeny: Biochemical and histopathological studies

The 2,4‐Dichlorophenoxyacetic acid (2,4‐D) was used in agriculture as an herbicide in many countries including Tunisia. The aim of this study was to evaluate the effects of 2,4‐D on liver function of adult rats and their progeny. Female Wistar rats were divided into two groups: the controls and the treated rats which received 600 ppm of 2,4‐D in their drinking water from the 14th day of pregnancy until day 14 after delivery. In 2,4‐D group, a significant decrease in body weight of pups was noted, when compared to controls. Liver antioxidant enzyme activities, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) decreased, while malondialdehyde (MDA) levels increased in dams and pups. Moreover, plasma aminotransferases (ALT, AST), gamma glutamil transpeptidase (GGT), lactate dehydrogenase (LDH), bilirubin and albumin levels were increased significantly. The biochemical modifications were correlated with histopathological studies. We concluded that 2,4‐D induced hepatotoxicity in adult and suckling rats.

Anti-oxidant, anti-inflammatory, analgesic and antipyretic activities of grapevine leaf extract (Vitis vinifera) in mice and identification of its active constituents by LC–MS/MS analyses

ETHNOPHARMACOLOGICAL RELEVANCE The leaves of Vitis vinifera is used in traditional medicine for diarrhea, hepatitis and stomachaches. The objective of this study was to investigate the anti-oxidant, anti-inflammatory, analgesic and antipyretic properties of the hydroalcoholic leaf extract of Vitis vinifera (EVV) on experimental models to provide scientific basis for its use. MATERIALS AND METHODS The EVV was chemically characterized by LC-MS/MS analyses. The in vitro antioxidant activities of the EVV extract were measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay and Ferric reducing antioxidant power assay (FRAP). Analgesic activity using acetic acid induced writhing and formalin test in mice, anti-inflammatory activity using carrageenan induced paw oedema and acetic acid-induced vascular permeability in mice, and antipyretic activity using Brewers yeast induced pyrexia in rats were evaluated at 100mg/kg, 200mg/kg, and 400mg/kg doses of the extract. RESULTS The extract (EVV) was found to contain resveratrol, quercetin, catechin, flavone, flavonols, anthocyanin, gallic acid and epicatechin. EVV produced significant dose-response anti-inflammatory activity against carrageenan-induced paw edema. EVV at dosages of 100, 200 and 400mg/kgbw significantly reduced carrageenan-induced paw edema by 34.48% (P<0.05), 36.20% (P<0.05), and 41.37% (P<0.05) at 5h after carrageenan injection, respectively. Also EVV extract reduces significantly acetic acid-induced vascular permeability in mice dose dependently. EVV (100, 200 and 400mg/kgbw) produced significant dose-response analgesic activity in the formalin test. However, the low percentage inhibition (50%) suggests that it is not a centrally acting analgesic. Extract at dosages of 100, 200 and 400mg/kg bw, p.o. significantly reduced acetic acid-induced writhing by 48.15% (p<0.05), 57.97% (p<0.05), and 68.09% (p<0.05), respectively. The extract also caused marked dose-dependent inhibition of formalin-induced pain in the second phase (p<0.05). Statistical significant reduction in rectal temperatures was observed in standard group at 21 and 23h, and in 200mg/kg and 400mg/kg doses of the extract at 23h (p<0.05) compared with the 19h. CONCLUSIONS The results obtained indicated potential analgesic, anti-inflammatory and antipyretic effects of them hydroalcoholic leaf extract of V. vinifera observed at doses tested which support the claim for the traditional use of the plant in the treatment of various inflammatory and pain diseases.

Oxidative stress and thyroid impairment after gibberellic acid treatment in pregnant and lactating rats and their offspring

Gibberellic acid (GA₃) has been worldwide used in agriculture as a plant growth regulator. The purpose of this study is to assess the effects of GA₃ on the morphology and the thyroid hormone levels in adult rats and their suckling pups. Animals were given daily 200 ppm GA₃ in drinking water from the 14th day of pregnancy until day 14 after delivery. Compared with a control group, GA₃-treated mothers and pups showed an increase in body and thyroid weights, a decrease in plasma FT₄ and FT₃ levels, which were more pronounced in pups than in their mothers. Thyroid iodine content was also decreased in pups. These biochemical modifications corresponded histologically; the majority of follicles had cubical epithelial cells, which surrounded empty vesicular cavities. Toxicity was objectified by a significant increase in plasma malondialdehyde, protein carbonyls, and advanced oxidation protein products levels in GA₃-treated dams and their suckling pups; while, the activities of superoxide dismutase, catalase, and glutathione peroxidase were decreased in plasma of both dams and their pups. Moreover, a significant decline was observed in plasma glutathione, nonprotein thiols, and vitamin C levels. We conclude that GA₃ treatment affects thyroid function and plasma antioxidant status in adult rats and their progeny.