BAAE-AgNPs Improve Symptoms of Diabetes in STZ-induced Diabetic Rats.

OBJECTIVES: Nanoparticles can be employed to improve the therapeutic activity of natural products. Type 2 diabetes mellitus is a serious health condition that has spread like a "modern pandemic" worldwide. In the present study, we developed silver nanoparticles, Ag-NPs, with an aqueous extract from Balanites aegyptiaca to investigate their antioxidant and anti-inflammatory activity in STZ-induced diabetic rats. METHODS: Aqueous extracts of Balanites aegyptiaca seeds (BAAE) were used in the synthesis of BAAE-AgNPs, which were characterized using FTIR and TEM. Different doses of BAAE-AgNP (1/50 LD50; 29.4 mg/kg b.w. and 1/20 LD50: 73.5 mg/kg b.w.) were administered to STZ-induced diabetic rats to evaluate their potential antidiabetic activity. RESULTS: FTIR spectral data indicated the presence of flavonoids and polyphenols in BAAEAgNPs. The size of the BAAE-AgNPs, determined by TEM examination, was 49.33 ± 7.59 nm, with a zeta potential of +25.37. BAAE-AgNPs were characterized by an LD50 value of 1470 mg/kg b.w. In diabetic rats, the daily oral administration of both doses of BAAE-AgNPs (29.4 and 73.5 mg/kg b.w.) for 12 weeks resulted in a significant improvement in body weight, insulin homeostasis, HbA1c, HDL-C, MDA, and pancreatic SOD, CAT, and GSH. They reduced plasma glucose, cholesterol, and triglycerides. This treatment also resulted in a significant decrease in pancreatic IL-6, p53, and TNF-α in diabetic rats. Furthermore, BAAE-AgNPs down-regulated pancreatic TGF-ß1 and Akt gene expression in diabetic rats and resulted in a significant decrease in the regulation of hepatic GLUT-2, as well as an increase in the regulation of hepatic GK and pancreatic B-cl2 gene expression. The histopathological results obtained indicated that BAAEAgNPs improved pancreatic tissue metabolism by enhancing antioxidant enzymes, suppressing inflammatory cytokines, and scavenging free radicals. CONCLUSION: The findings implied that similar to the glibenclamide-treated groups, in the BAAEAgNPs treated group, the compromised antioxidant status normalized in STZ-induced diabetes. By scavenging free radicals, BAAE-Ag-NPs protected against lipid peroxidation while reducing the risk of complications from diabetes. Compared to the daily dose of 29.4 mg, the impact was more prominent at 73.5 mg.

The potential hazardous effect of exposure to iron dust in Egyptian smoking and nonsmoking welders.

Exposure to iron dust and welding fumes is widespread and may increase the risk of lung inflammation. The aim of this study was to identify associations between exposure to iron/welding fumes and the levels of inflammatory parameters and allergic mediators among 120 Egyptian men. Forty nonsmoking and 40 smoking Egyptian welders as well as 40 healthy volunteers who were never exposed to welding fumes and were nonsmoking were enrolled in the study. Peak expiratory flow rates (PEFR) assessed at the end of the shift of work on working days revealed an impairment in lung function, with the smoking workers showing the worse results, followed by nonsmoking workers, as compared to healthy volunteers. Moreover, the results of the present study showed a significant increase in serum iron and immunoglobulin E, as well as plasma thiobarbaturic acid reactive substances, C-reactive protein, tumor necrosis factor-alpha, haptoglobin, interleukin-2, interleukin-6 and interleukin-23 histamine, lactate dehydrogenase isoenzyme-3, and calcitonin. In addition, the results revealed significant decrease in plasma α-1-antitrypsin and serum transferrin, as well as blood activities of antioxidant enzymes: catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase (as compared with control group). However, there was a nonsignificant change in arginase and α-L-fucosidase in smoking and nonsmoking welders exposed to iron dust and welding fumes. In conclusion, occupational exposure to iron dust and welding fumes increases lung inflammation risk among Egyptian blacksmith workers, a condition that worsens with smoking.

Synthesis of Cinnamyl and Caffeoyl Derivatives of Cucurbitacin-Eglycoside Isolated from Citrullus colocynthis Fruits and their Structures Antioxidant and Anti-inflammatory Activities Relationship.

BACKGROUND: Citrullus colocynthis (L.) Schrad is an important medicinal plant belonging to the family Cucurbitaceae. Cucurbitacin E glucoside (1) was isolated from Citrullus colocynthis fruits. A novel mono-ester of cucurbitacin-E and cinnamyl and caffeoyl-ß-D-glucoside (2 and 3) was synthesized by reaction of cucurbitacin E glucoside with cinnamic and/or caffeic acid in the presence of CHCl2 and K2CO3 with constant stirring with an ice-cooling state for 24h. Mass analyses of the isolated and purified compounds were determined. METHODS: The elemental analysis (C, H, N) suggesting the molecular formulae of the compounds (1-3) to be C38H54O13, C47H60O14, and C47H60O16; respectively. I.R., 1H-NMR, and 13C-NMR analyses were recorded. The median lethal doses (LD50s) of compounds (1-3) in rats were 1262.5, 2500 and 2350 mg/kg b.w., respectively. The anti-inflammatory, total antioxidant, reducing power, anti-reactive oxygen species (ROS) and anti-reactive nitrogen species (RNS) were more pronounced in compound 3 compared to compounds (1-2). This study provides the scientific basis for the anti-inflammatory effects of the isolated cucurbitacin E glucoside (1) and its derivatives (2 and 3) in a t-BHP (tert-butyl hydrogen peroxide)-induced liver damage model. RESULTS: Injection of rats with t-BHP (1.8 mmol/kg) showed a significant increase in plasma alanine transaminases (ALT), aspartate transaminases (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and malondialdehyde (MDA) as well as hepatic tumor Necrosis Factor-α (TNF-α), interleukin- 6 (IL-6) and interleukin-23 (IL-23) when compared with control group. Also, injection of rats with t-BHP showed a significant increase in a liver level of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) as compared with control group. Oral administration of cucurbitacin E glucoside (1) and its derivatives (2 and 3) at a concentration of 25 and 50 mg/kg b.wt daily for 5 days showed a significant protection against-induced alteration in liver GSH, SOD, CAT and GST as well as plasma ALT, AST, ALP, LDH and MDA levels. Furthermore, Cucurbitacin E glucoside (1) and its derivatives (2 and 3) inhibited the elevation of proinflammatory cytokines (TNF-α, IL-6, and IL-23) in the livers of t-BHP-treated rat models. CONCLUSION: These results suggested that mechanistic-based evidence substantiating the traditional claims of cucurbitacin E glucoside (1) and its derivatives (2 and 3) to be applied for the treatment of inflammation-related disorders, such as oxidative liver damage and inflammation diseases.

Astaxanthin; a Promising Protector Against Gentamicin-Induced Nephrotoxicity in Rats.

Gentamicin is an aminoglycoside antibiotic widely used against infections caused by Gram-negative microorganisms. Nephrotoxicity is the main limitation to its therapeutic use. The objective of this study was to evaluate the potential protective effect of astaxanthin on the renal damage generated by gentamicin in rats, in an attempt to understand its mechanism of action, which may pave the way for possible therapeutic applications. The daily oral administration of the astaxanthin at a concentration of 50 mg/kg for 15 days to gentamicin (80 mg/kg.b.w) treated rats showed a significant decrease (p<0.05) in plasma creatinine, urea, TNF-α as well as plasma and renal MDA and HP. The treatment also resulted in a significant increase in hemoglobin, plasma sodium, potassium and TAS as well as renal total protein, GSH, Pr-SHs, G6PD, SOD, GPx, CAT and GR levels. The histological examinations of renal tissues in this study revealed damage and glomerular infiltration in gentamicin treated rats. The presented data suggest that astaxanthin has a significant prophylactic action against gentamicin-induced nephrotoxicity in rats. The effect was more pronounced in case of astaxanthin pre-treatment compared with administration of astaxanthin post-treatment. Taken together, astaxanthin has a potential as a protective and therapeutic agent for nephrotoxicity and deserves clinical trial in the near future as an adjuvant therapy in patients treated with gentamicin.