Platelet-rich plasma and/or sildenafil topical applications accelerate and better repair wound healing in rats through regulation of proinflammatory cytokines and collagen/TGF-ß1 pathway.

Platelet-rich plasma (PRP) composites of various cytokines and growth factors which have the potential to activate and speed the process of wound repair. Sildenafil also is a potent stimulator of angiogenesis which favors its potential effects on wound healing in several models. Existing work planned to examine the effectiveness of topical application of PRP and/or sildenafil citrate hydrogel (SCH) in a non-splinted excision skin wound model. Adult male rats were allocated into control, PRP, SCH, and PRP/SCH groups. On the 7th and 14th days, blood and tissue samples were collected for hematobiochemical, histopathological, and immunohistochemistry analyses. PRP and/or SCH topical treatments caused an enhancement of wound healing parameters, including a rapid switch from inflammatory phase to connective tissue stage evident by less systemic hematological changes and decreased values of proinflammatory cytokines (IL-6, TNF-α, and IL-1ß) and C-reactive protein (CRP) on the 7th or 14th days post-wounding. Also, tissue hydroxyproline, collagen, nitrite, and total protein contents were higher in therapeutically handled wounded rats. Histologically, PRP- and/or SCH-treated wounded rats exhibited less necrosis, inflammation, and fibrin with a higher level of granulation tissue formation on the 7th day post-wounding and abundant collagen remodeling, epithelization, and vascularization on the 14th day relative to control. Interestingly, combined PRP and SCH treatment was more efficient in wound healing scoring with less inflammation, more collagen remodeling, and more epithelization. Our findings confirm the effectiveness of PRP and/or SCH as a topical wound healing treatment, with better skin wound healing with their combination.

The effect of lipoic acid on acrylamide-induced neuropathy in rats with reference to biochemical, hematological, and behavioral alterations.

CONTEXT: Acrylamide (ACR) is a well-known neurotoxicant and carcinogenic agent which poses a greater risk for human and animal health. OBJECTIVE: The present study evaluates the beneficial effects of α-lipoic acid (LA) on ACR-induced neuropathy. MATERIALS AND METHODS: A total of 40 male rats were divided into four groups: a placebo group; LA-treated group, administered orally 1% (w/w) LA mixed with diet; ACR-treated group, given 0.05% (w/v) ACR dissolved in drinking water; and LA + ACR-treated group, given LA 1% 7 d before and along with ACR 0.05% for 21 d. After 28 d, blood samples were collected, the rats were decapitated, and the tissues were excised for the measurement of brain biomarkers, antioxidant status, and hematological analysis. Also, the gait score of rats was evaluated. RESULTS: ACR-exposed rats exhibited abnormal gait deficits with significant (p < 0.05) decline in acetylcholine esterase (AChE) and creatine kinase in serum and brain tissues, respectively. However, the lactate dehydrogenase activity was increased in serum by 123%, although it decreased in brain tissues by -74%. ACR significantly (p < 0.05) increased the malondialdehyde level by 273% with subsequent depletion of glutathione S-transferase (GST), glutathione peroxidase (GPx), and glutathione reductase (GR) activities and reduced the glutathione (GSH) level in brain tissue. Interestingly, LA significantly (p < 0.05) improved brain enzymatic biomarkers, attenuated lipid peroxidation (LPO), and increased antioxidant activities compared with the ACR-treated group. DISCUSSION AND CONCLUSION: These results suggested that LA may have a role in the management of ACR-induced oxidative stress in brain tissues through its antioxidant activity, attenuation of LPO, and improvement of brain biomarkers.

Effect of sildenafil citrate (Viagra®) on trace element concentration in serum and brain of rats.

As a vasodilator with good hemodynamic effects, sildenafil has been successfully used in the treatment of patients with pulmonary hypertension and cardiovascular diseases. By selectively inhibiting phosphodiestrase type 5 (PDE-5) and thus effectively reducing the breakdown of c GMP, sildenafil administration can markedly improve the erectile dysfunction. Sildenafil also elevates localized cerebral blood flow in rat brain. The objective of the present study was to investigate the effect of sildenafil on the level of trace elements (Zinc (Zn), copper (Cu), iron (Fe), selenium (Se), cobalt (Co), and chromium (Cr)) in blood and brain of rats. Sixteen male albino rats weighing 180-200 g were divided into two groups (8 rats/group). Sildenafil (Viagra, Pfizer Inc.) was dissolved in saline and administered at a dose of 10mg/kg i.p. (0.5 ml volume) to rats in the treated group every 72 h for 12 injections. Rats in the control group were administered the same volume of saline as in treated group. All rats were sacrificed 24h after the last injection. Blood samples were collected and serum was separated and stored at -20°C. Brains were dissected and stored frozen until analysis. Trace elements concentrations were determined by flame emission atomic absorption spectrophotometer. Results showed that sildenafil injection significantly (P<0.05) increased serum and brain Se and Cu concentrations. Moreover, sildenafil increased the Cr concentration in the brain tissue. It was concluded that sildenafil citrate administration increased serum Se and Cu as well as, increased brain Se, Cu, and Cr concentrations in rats.

Grape seed extract prevents azathioprine toxicity in rats.

Azathioprine (Aza) is an important drug commonly used in the therapy of autoimmune system disorders. It induces hepatotoxicity and hazard effects that restrict its use. The effects of administration of grape seed extract and folic acid on Aza toxicity by gavage (simultaneously) daily for 4 weeks were studied by determining the changes in some hematological parameters and liver histology. The glutathione level (GSH) and lipid peroxidation content as malondialdehyde (MDA) in the liver tissue were measured. The repeated intake of Aza (25 mg/kg body weight) induced anemia characterized by decreased erythrocyte and leukocyte counts and reticulocyte and hematocrit percentages, while the prothrombin time was significantly increased. Moreover, Aza caused a significant decrease in phagocytic activity and lymphocyte percentage. Aza induced hepatic damage as indicated by pronounced changes in the histological structure, a significant increase in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), and MDA content in the liver tissue. Meanwhile, the GSH activity was significantly decreased. Co-treatment with grape seed extract and Aza minimized the previously mentioned hazard effects of Aza and significantly protected the hepatic tissue by ameliorating the antioxidant activity. Folic acid administration, simultaneously, with Aza only improved the anemia. It may be concluded that grape seed extract is a useful herbal remedy, especially for controlling oxidative damages and is considered as a potent protective agent against Aza hepatotoxicity.