Centella asiatica Improves Kim-1, eNOS and GPX-1 Kidney mRNA Expression in Diabetes Mellitus Rat Model

@#Introduction: Diabetic nephropathy is one of the most common complications in diabetes Mellitus. Hyperglycemia and chronic inflammation cause abnormal oxidative stress deposition that leads to the decrease of glutathione peroxidase-1 (GPx1) and endothelial Nitric Oxide synthetase (eNOS). It was reported that Centella asiatica has an anti-hyperglycemic and anti-inflammatory effect. However little is known about Centella asiatica effect in the kidney of DM. The objective of this study was to know the effect of Centella asiatica extract on Kim-1 (marker of kidney damage), GPx1 and eNOS mRNA expression in the kidney of DM rat model. Methods: Wistar DM rat model was divided into 6 groups namely non-DM group, DM group , DM with captopril and another DM group treated with Centella asiatica with three different dosages (250, 500 and 1000 mg/kg BW). The treatment was given for 8 weeks. The Kim-1, GPx1 and eNOS expression was measured using semi-quantitative PCR. Results: The DM group showed higher Kim-1 kidney mRNA expression but lower GPx1 and eNOS kidney mRNA compare to those on the non-DM group. Administration of Centella asiatica improves the expression of Kim-1, GPx1 and eNOS kidney mRNA expression in DM rat model. Conclusion: Centella asiatica has the potential to prevent kidney damage in DM rat model by improving Kim-1, GPx1 and eNOS kidney mRNA expression.

Effect of Cimetidine on the Histopathology and the Expression of SOD2 and GPX1 in Low-dose Accumulative Irradiated Beagle Dogs Spleen / 中国药学杂志

OBJECTIVE: To study the effect of cimetidine on the histopathology and the expression of SOD2, GPX1 gene and protein in low-dose accumulative irradiated Beagle dogs spleen and to investigate the mechanism of cimetidine′s protective effect on low-dose accumulative irradiation. METHODS: Twenty-four male Beagle dogs were divided into six groups: normal control group,model group,positive drug control group and cimetidine groups at the dose of 5.33, 10.67, 21.33 mg•kg-1 respectively. The dogs were irradiated with 60Co-γ-ray at 0.040 8 mGy•min-1 rate for 23 d. Cimitidine was administered intragastrically during irradiation, once a day. Microscope was adopted to observe the pathologic change of spleen and the expression levels of SOD2,GPX1 gene and protein in the spleen tissue of dogs were detected by qRT-PCR and immunohistochemistry techniques. RESULTS: Compared with the model group,cimetidine ameliorated the pathological changes and ultrastructure lesions in the spleen of dogs. Also compared with the model group, the levels of SOD2 and GPX1 protein in cimetidine groups at the dose of 5.33, 10.67, 21.33 mg•kg-1 were higher(P<0.05) and the levels of SOD2 and GPX1 mRNA of the three cimetidine groups were increased significantly(P<0.01). CONCLUSION: Cimetidine can reduce the histological damage. Cimetidine can upregulate the expressions of SOD2 and GPX1 gene and protein and it has good protective effect on the antioxidant system injury.

Anti-aging effects and mechanism of red ginseng extract on d-galactose induced aging mice / 中国药学杂志

OBJECTIVE: To investigate the protective mechanism of red ginseng extract(RG) on aging mice induced by D-galactose and the correlation between tumor necrosis factor-α (TNF-α)glutathione peroxidase 1 (GPX1), glutathione peroxidase 2 (GPX2), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-10 (IL-10). METHODS: Aging mice models were caused by D-galactose and randomly divided into control group, model group, RG low, medium and high dose (100, 200, 400 mg•kg-1) groups. The preparation of model and drug delivery, after 42 d, the mice were killed and determination of spleen index; the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and brain tissue were measured. In serum, the levels of acetylcholinesterase (AChE), catalase (CAT), glutathione peroxidase (GSH-PX), inducible nitric oxide synthase (i-NOS) were measured. Enzyme-linked immunosorbent assay (ELISA) was used to test the levels of cyclooxygenase-2 (COX-2), TNF-α, IL-1β and IL-6 in brain tissue. Real time quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect the correlation of TNF-α, GPX1, GPX2, IL-1β, IL-6 and IL-10 gene mRNA expression in brain tissue. RESULTS: The RG can enhance the spleen index, increase the activity of SOD in serum and brain tissue and AChE, CAT and GSH-PX in serum, decrease the content of MDA in serum and brain tissue, and decrease the content of iNOS in serum and the content of COX-2, TNF-α, IL-1β and IL-6 in brain tissue. At the same time, it significantly inhibited the mRNA expression of TNF-α, IL-1β and IL-6 in the brain tissue of mice, and increased the expression of GPX1, GPX2 and IL-10 mRNA in the brain tissue, and had statistical significance. CONCLUSION: Concentrated solution of red ginseng extract could significantly exhibit anti-aging effects, its mechanism may be related to the TNF-α, GPX1, GPX2, IL-1β, IL-6 and IL-10 expression in aging, enhancing immune function, and removing free radicals and inflammatory factor.

Protective effects of silymarin on methotrexate-induced damages in rat testes

Abstract The present study aimed to investigate the protective effects of silymarin (SMN), an antioxidant, on methotrexate (MTX)-induced damage in rat testes. Thirty-two Wistar albino rats were divided into four groups (n = 8): control, MTX (20 mg/kg, i.p. on days 1 and 5), SMN (200 mg/kg, orally), and MTX + SMN (20 mg/kg, i.p. on days 1 and 5 and SMN 200 mg/kg orally) groups. At the end of the 6-week trial period, histopathological, immunohistochemical, biochemical, and spermatological analyses were performed on testes tissues. Histopathologically, MTX-induced damage, including depletion of germ cell and loos of spermatozoa, was significantly improved with SMN treatment. Immunohistochemically, the immunoreactivity of glutathione peroxidase 1 (GPx1) and manganese superoxide dismutase 2 (SOD2) were detected more intensely in the MTX + SMN group than in the MTX group. Biochemical examinations revealed that SMN supplementation decreased the lipid peroxidation and increased enzymatic antioxidants in the SMN-treated rats. Spermatologically, significant differences were found in the density, motility, dead-to-live sperm ratio, and abnormal sperm rate in the MTX + SMN group compared to the MTX group. In conclusion, SMN seems to have protective effects as an antioxidant against MTX-induced damage in rat testes.

Association of the Superoxide Dismutase (V16A) and Catalase (C262T) Genetic Polymorphisms with the Clinical Outcome of Patients with Acute Paraquat Intoxication

BACKGROUND/AIMS: Many patients with acute paraquat (PQ) intoxication die even at low PQ concentrations, whereas others with similar concentrations recover. Therefore, it is possible that individual differences in antioxidant capacity are responsible for the variable clinical outcome in patients with acute PQ intoxication. METHODS: We investigated whether there was a relationship between the genetic polymorphisms of SOD (V16A), catalase (C262T), and GPX1 (C593T) in 62 patients with acute PQ intoxication and the clinical outcomes of these patients. RESULTS: The frequency of the Mn-SOD V/V, V/A, and A/A genotypes were 56.3, 43.5, and 0% in survivors and 86.9, 13.1, and 0% in non-survivors (p > 0.05). The GPX1 C/C, C/T, and T/T genotypes were present in 100, 0, and 0% of all subjects. The catalase C/C, C/T, and T/T genotypes were present in 100, 0, and 0% of survivors, and in 82.6, 17.4, and 0% of non-survivors. Neither erythrocyte SOD activity nor catalase activity were significantly different between survivors and non-survivors. CONCLUSIONS: No association was found between clinical outcome of acute PQ intoxication and the genetic polymorphism of GPX1 (C593T) or the genetic polymorphisms or enzyme activity of superoxide dismutase (V16A) or catalase (C262T).

Construction and identification of recombination expression vector Ksp-Cadherin-Gpx1-Kik1 / 药物分析学报

Objective To construct and identify the Gpx1-Klk1 vector which contains kidney-specific promoter (Ksp-cadherin). Methods Through PCR amplification, the human Gpx1, Klk1, and Ksp-cadherin eDNA were obtained by taking Gpx1 cDNA, Klk1 eDNA, and Ksp-cadherin BAC as templates. After being testified, the PCR products were inserted into the expressive vector pIRES-EGFP step-by-step to produce a recombinant vector Ksp-cadherin-Gpx1-Klk1. This vector was examined by restriction enzyme digestion and sequence analysis. Results The recombinant expressive vector Ksp-cadherin-Gpx1-Klk1 was successfully constructed. Conclusion The construction of the recombinant vector Ksp-cadherin-Gpx1-Kik1 laid foundations for investigations in establishing transgenic animal models, the over-expression of Gpx1 and Kikl in mammal kidney, and gene therapy for ischemia-reperfnsion injury during kidney transplantation.