Role of nitric oxide in mediating the cardioprotective effect of agomelatine against isoproterenol-induced myocardial injury in rats.

Myocardial infarction (M/I) is a common cause of mortality worldwide. Agomelatine (AGO), a potent melatonin receptor agonist, proved to have an anti-inflammatory and antioxidant effect. The present study aimed to explore the cardioprotective effect of AGO on isoproterenol (ISO)-induced myocardial injury in a rat model and determine the role of nitric oxide (NO) in mediating this beneficial effect. Rats were randomly divided into 6 groups and treated for 12 days. Group 1, control, received normal saline. Group 2, ISO group, received ISO (100 mg/kg, i.p.) in 11th and 12th days. Group 3, positive control group, received atenolol (100 mg/kg/day) + ISO. Group 4, AGO-treated group, received AGO (80 mg/kg/day) + ISO. Group 5, L-NNA + ISO, received L-NG-nitro arginine (L-NNA) (25 mg/kg, orally) + ISO. Group 6, AGO + L-NNA + ISO, co-treated with AGO + ISO + L-NNA. Serum cardiac enzymes and cardiac tissue oxidative stress parameters were assessed along with histopathological evaluation. Gene expression quantification of nuclear factor erythroid 2 (Nrf-2) and heme oxygenase-1 (HO-1) were assessed. Immunoexpression of inducible NO synthase (iNOS) and caspase-3 were evaluated. The outcomes proved that ISO significantly increased serum cardiac enzymes, with histopathological changes of myocardial tissue along with a major increase in oxidative, inflammatory, and nitrosative stress, besides a reduction in cardiac Nrf-2 and HO-1 gene expressions with marked myocardial cell apoptosis. However, pretreatment with AGO significantly reversed these profound ISO myocardial damaging effects. AGO protects against ISO-induced myocardial injury through its antioxidant, anti-inflammatory, and anti-apoptotic effects with modulation of NOS enzymes.

Therapeutic effect of liraglutide on expression of CTGF and BMP-7 in induced diabetic nephropathy.

INTRODUCTION: Diabetic nephropathy (DN) is one of the critical complications of diabetes mellitus and the main cause of chronic renal dysfunction. The pathogenic mechanism causing the disease remains unclear and there is a lack of effective treatment methods so novel strategies are needed for DN management. The aim of this study, therefore, is to evaluate the effect of liraglutide as glucagon-like peptide-1 analogue and its underlying mechanisms on induced DN in rats MATERIALS AND METHODS: Sixty rats were divided into control group, diabetic group, and liraglutide-treated group. At the end of experiment, renal CTGF and BMP-7 messeger RNA expression were determined. Blood sugar, serum urea, and creatinine were measured. Also, histopathological changes were studied. RESULTS: Liraglutide can improve renal alterations associated with diabetes as it reduced CTGF expression and increased BMP-7 expression. In the same time, it could improve histopathological changes and renal function tests. CONCLUSION: These findings influence the beneficial use of liraglutide for the management of DN in patients with diabetes mellitus.

Mechanisms of Thymoquinone Hepatorenal Protection in Methotrexate-Induced Toxicity in Rats.

To investigate mechanisms by which thymoquinone (TQ) can prevent methotrexate- (MTX-) induced hepatorenal toxicity, TQ (10 mg/kg) was administered orally for 10 days. In independent rat groups, MTX hepatorenal toxicity was induced via 20 mg/kg i.p. at the end of day 3 of experiment, with or without TQ. MTX caused deterioration in kidney and liver function, namely, blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase. MTX also caused distortion in renal and hepatic histology, with significant oxidative stress, manifested by decrease in reduced glutathione and catalase, as well as increase in malondialdehyde levels. In addition, MTX caused nitrosative stress manifested by increased nitric oxide, with upregulation of inducible nitric oxide synthase. Furthermore, MTX caused hepatorenal inflammatory effects as shown by increased tumor necrosis factor-α, besides upregulation of necrosis factor-κB and cyclooxygenase-2 expressions. MTX also caused apoptotic effect, as it upregulated caspase 3 in liver and kidney. Using TQ concurrently with MTX restored kidney and liver functions, as well as their normal histology. TQ also reversed oxidative and nitrosative stress, as well as inflammatory and apoptotic signs caused by MTX alone. Thus, TQ may be beneficial adjuvant that confers hepatorenal protection to MTX toxicity via antioxidant, antinitrosative, anti-inflammatory, and antiapoptotic mechanisms.

Prevalence of methicillin resistant Staphylococcus aureus among Egyptian patients after surgical interventions.

BACKGROUND: Staphylococcus aureus (S. aureus) is isolated frequently from surgical site infections and other soft tissue infections. There are limited data examining the prevalence of methicillin resistant S. aureus (MRSA) among Egyptian patients after surgery. The current study determined the prevalence of MRSA isolated from surgical site and soft tissue infections at Minia University Hospital (MUH), determined their susceptibility to ß-lactams and other antimicrobials, and examined their mecA gene expression. METHODS: A total of 208 hospitalized patients attending the General Surgery Department at MUH were enrolled and all had skin and soft tissue infections (SSTIs) of different causes. These 208 patients (143 males and 65 females) were suffering from surgical site infection (SSI; n=82), diabetic foot (n=52), abscess (n=45), or burn (n=29) infections. Samples were cultured on different media for isolation and identification of S. aureus and the isolates were screened for antibiotic susceptibility. All MRSA isolates were tested by polymerase chain reaction to detect the mecA gene responsible for methicllin resistance. RESULTS: 241 Staphylococcal species represented the most common isolates (64.8%) among 371 collected isolates from the 208 patients. Out of the 241 staphylococcal isolates, 127 were S. aureus (61% of the total patients). The prevalence of S. aureus among SSI, diabetic foot, abscess, and burn patients were 59%, 75%, 56%, and 52%, whereas that of MRSA was 16%, 17%, 13%, and 10%, respectively. MRSA isolates (n=31; 15% of patients) showed multiple resistance to at least one member of the antimicrobial groups tested with an average resistance to 6.6±1.9 antimicrobial groups. Polymerase chain reaction data showed that only 29 isolates of the MRSA isolates (94%) were positive for mecA gene. CONCLUSIONS: Staphylococcus aureus isolates are the major pathogens responsible for wound and surgical site infections at MUH and MRSA are a potential threat for wound patients in Egypt.

Protective effects of curcumin, alpha-lipoic acid, and N-acetylcysteine against carbon tetrachloride-induced liver fibrosis in rats

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Liver fibrosis is a major health problem that can lead to the development of liver cirrhosis and hepatocellular carcinoma. On the other hand, several antioxidants have been shown to possess protective effect against liver fibrosis. Therefore, in the present work, the effectiveness of curcumin, alpha-lipoic acid, and N-acetylcysteine in protecting against carbon tetrachloride (CCl4)-induced liver fibrosis as well as the mechanism(s) implicated in this protective effect was studied. The antioxidants used in this study resulted in hepatoprotective effect as evident by substantial (..) (AU)

Protective effects of curcumin, α-lipoic acid, and N-acetylcysteine against carbon tetrachloride-induced liver fibrosis in rats.

Liver fibrosis is a major health problem that can lead to the development of liver cirrhosis and hepatocellular carcinoma. On the other hand, several antioxidants have been shown to possess protective effect against liver fibrosis. Therefore, in the present work, the effectiveness of curcumin, α-lipoic acid, and N-acetylcysteine in protecting against carbon tetrachloride (CCl(4))-induced liver fibrosis as well as the mechanism(s) implicated in this protective effect was studied. The antioxidants used in this study resulted in hepatoprotective effect as evident by substantial decreases in collagen deposition in histopathological examinations in addition to significant decrease in serum levels of alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transpeptidase, bilirubin, and transforming growth factor-alpha (TGF-α) as well as hepatic malondialdehyde concentration, with a concurrent increase in serum matrix metalloproteinase-13 (MMP-13) and hepatic reduced glutathione (GSH) levels as compared to CCl(4) fibrotic group. In conclusion, curcumin, α-lipoic acid, and N-acetylcysteine protect rats against CCl(4)-induced liver fibrosis most possibly through their antioxidant activities and their capacities to induce MMP-13 and to inhibit TGF-α levels.