The Protective Effects of Thymosin-ß-4 in a Rat Model of Ischemic Acute Kidney Injury.

BACKGROUND: Despite the progress in the treatment of acute kidney injury (AKI), current curative approaches fail to provide adequate treatment. In this study, we aimed to investigate the possible protective effects of thymosin-ß-4(Tß4) on an ischemic AKI model in rats. METHODS: Rats were randomly assigned into four groups (n = 8/group): The control group (sham-operated), the ischemia-reperfusion (I/R) group; renal ischemia (90 min) by infrarenal abdominal aortic occlusion followed by reperfusion (3 h), the Tß4 + I/R group; treated with Tß4 before I/R, and the I/Tß4/R group; treated with Tß4 just before reperfusion. Besides renal function determination (creatinine (Cr) and blood urea nitrogen (BUN)); histological evaluation was also conducted. Renal tissue caspase-9, matrix metalloproteinase (MMP-9) activities, and hyaluronan levels were measured. Additionally, renal tissue oxidative stress (lipid hydroperoxide, malondialdehyde, superoxide dismutase, glutathione, pro-oxidant-antioxidant balance, ferric reducing antioxidant power, nitric oxide), inflammation (tumor necrosis factor-α, interleukin-1ß, interleukin-6, nuclear factor-κß) were evaluated. RESULTS: I/R increased the level of caspase-9, MMP-9 activity, and hyaluronan (p < 0.001) and these were significantly decreased in both Tß4 groups. Moreover, I/R led to increases in oxidative stress and inflammation parameters (p < 0.001) while the levels of antioxidants were decreased. Nevertheless, Tß4 in both groups were able to restore oxidative stress and inflammation parameters. Furthermore, Tß4 attenuated histologic injury caused by I/R (p < 0.01) and diminished serum urea-creatinine levels (p < 0.001). CONCLUSION: These results suggest that Tß4 has significant improving effects in ischemic acute kidney injury. This beneficial effect might be a result of the inhibition of extracellular matrix remodeling and apoptosis cascade via modulation in renal redox status and inflammation.

Resveratrol can prevent CCl4-induced liver injury by inhibiting Notch signaling pathway.

We investigated whether Notch signaling was increased in an experimental liver fibrosis model and examined the effects of resveratrol on Notch expression. Rats were divided into four groups: the control group, injected with physiological saline; the CCl4 group; the CCl4 plus resveratrol group; and the resveratrol group. After treatment, immunostaining was performed to detect Notch1, Notch3, Notch4, transforming growth factor (TGF)-beta, alpha-smooth muscle actin (SMA), glial fibrillary acidic protein (GFAP), and proliferating cell nuclear antigen (PCNA), and TUNEL assays were performed to evaluate apoptosis. Sirius red staining was used to detect fibrosis. Samples were also biochemically evaluated for glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), lipid peroxidation, and protein oxidation. GSH, GPx, and catalase activities were significantly decreased (p⟨0.001) in the CCl4 group. Distinct collagen accumulation was detected around the central vein and portal areas, and numbers of Notch1-, Notch3-, and Notch4-positive cells were significantly increased (p⟨0.001) in fibrotic areas in the CCl4 group. Increased expression of Notch proteins in fibrotic areas may support the role of Notch in mediating signaling associated with liver fibrosis through activation of hepatic stellate and progenitor cells. In contrast, resveratrol prevented liver fibrosis by decreasing lipid peroxidation and may be effective for inhibiting Notch signaling.

The effect of Beta-aminopropionitrile and prednisolone on the prevention of fibrosis in alkali esophageal burns: an experimental study.

Objective. The aim of this study was to investigate the efficacy of beta-aminopropionitrile (BAPN) and prednisolone on the prevention of esophageal damage and stricture formation after caustic esophageal burn. Method. Twenty-eight rats were divided into four equal groups. In groups 1, 2, and 3, caustic esophageal burns were generated by applying NaOH to the 1.5 cm segment of the abdominal esophagus. Group 4 was for the sham. Normal saline to group 1, BAPN to group 2, and prednisolone to group 3 were administered intraperitoneally as a single daily dose. Results. Treatment with BAPN decreased the stenosis index (SI) and histopathologic damage score (HDS) seen in caustic esophageal burn rats. The SI in group 4 was significantly lower compared with groups 1, 2, and 3. Group 2 had the minimum SI value in corrosive burn groups. The differences related to SI between groups 1, 2, and 3 were not statistically significant. The HDS was significantly lower in group 4 compared with groups 1, 2, and 3. The HDS in group 2 was significantly lower compared with groups 1 and 3. Conclusion. This study demonstrated that BAPN was able to decrease the development of stenosis and tissue damage better than prednisolone.

Doxorubicin induced nephrotoxicity: protective effect of nicotinamide.

Introduction. Nephrotoxicity is one of the important side effects of anthracycline antibiotics. The aim of this study was to investigate the effects of nicotinamide (NAD), an antioxidant agent, against nephrotoxicity induced by doxorubicin (DXR). Methods. The rats were divided into control, NAD alone, doxorubicin (20 mg/kg, i.p.) and DXR plus NAD (200 mg/kg, i.p.) groups. At the end of the 10th day, kidney tissues were removed for light microscopy and analysis. The level of tissues' catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), inducible nitric oxide (iNOS) and endothelial nitric oxide (eNOS) activities were determined. Results. The activities of CAT, GPx, and GSH were decreased, and Po was increased in renal tissue of doxorubicin group compared with other groups. The tissue of the doxorubicin group showed some histopathological changes such as glomerular vacuolization and degeneration, adhesion to Bowman's capsule and thickening and untidiness of tubular and glomerular capillary basement membranes. Histopathological examination showed that NAD prevented partly DXR-induced tubular and glomerular damage. Conclusions. Pretreatment with NAD protected renal tissues against DXR-induced nephrotoxicity. Preventive effects of NAD on these renal lesions may be via its antioxidant and anti-inflammatory action.

The effects of valproic acid and levetiracetam on chicken embryos.

For patients with epilepsy, anti-epileptic medication is generally the first line of treatment, but treating pregnant women with epilepsy can be a challenge. Standard anti-epileptic medications have caused developmental abnormalities, so much effort has been put into developing antiepileptic medications with minimal teratogenic effects. In this experimental study, the new-generation anti-epileptic medication levetiracetam and the standard anti-epileptic medication valproic acid were compared in terms of teratogenicity by studying embryonic development in 360 fertile White-Leghorn chicken eggs (conception day 0). We found that levetiracetam may cause severe developmental abnormalities, and is likely not safe for use in pregnant women. As expected, valproic acid caused more frequent developmental abnormalities than levetiracetam, and the risk increased still further when both drugs were administered in combination. Levetiracetam should be used cautiously in pregnant women with epilepsy.