P53 Expression in Response to Equigan Induced Testicular Injury and Oxidative Stress in Male Rat and the Possible Prophylactic Effect of Star Anise Extracts

Objectives: Equigan is an anabolic androgenic steroid that developed for veterinary use to improve the food producing animal growth rate through promoting protein synthesis and muscle growth. The current study aimed to investigate the possible prophylactic effect of star anise extracts (SAE) response of to Equigan induced testicular injury, oxidative stress, P53 expression in male rats. Materials and Methods: Forty adult male rats were equally divided into four groups. 1st Control group, while 2nd group were rats receive orally SAE for 12 weeks. 3rd group include rats that injected intramuscularly with Equigan for 12 weeks while 4th group were co-treated group where rats injected with Equigan and SAE for 12 weeks. Results: Testis sections in Equigan treated rat induced abnormal arrangement of spermatogenesis cycles; disturbance and decrease in the spermatogenic cells, many of a syncytial cells were detected with marked decrease in sperms numbers and moderate depleted and degenerated Leydig cells. Testicular immunohistochemical observation after Equigan intramuscular injections showed a significant increase of the apoptotic protein p53. Co-administration of SAE with Equigan improved the testicular injury and P53 alternations. Conclusions: SAE could scavenge free radicals and produce beneficial effects against Equigan damage in testis and P53 alternations

Immunosuppressant drug tacrolimus induced mitochondrial nephrotoxicity, modified PCNA and Bcl-2 expression attenuated by Ocimum basilicum L. in CD1 mice

Tacrolimus (TAC) is used sporadically as an immunosuppressive agent for organ transplantation, but its clinical used is limited due to its marked nephrotoxicity. Ocimum basilicum L. (Lamiaceae) (OB) had been shown to possess antioxidant, anti-inflammatory and nephroprotective activity, and effective at improving renal inflammation and glomerular. In our study, we aim to evaluate the efficacy of the OB against TAC-induced mitochondrial nephrotoxicity in CD1 mice. Mice were randomly divided into four groups. Group 1 (control group); administered orally with normal saline (1 mL/kg) for two weeks; Group 2 (OB extract treated-group) (500 mg/kg b.wt) gavaged once/day for two weeks; Group 3 (TAC-treated group) (3 mg/kg b.wt, administered ip once a day for two weeks); and Group 4; (TAC plus OB extract treated-group). Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. The OB extract was high in phenolic content (50.3 mg/g of gallic acid equivalent), total flavonoids (14.5 mg/g CE equivalent). The potential antioxidant efficacy of the extract (IC50) was 24.5 μg/mL. OB pretreatment significantly improved the TAC-induced changes in biochemical markers of nephrotoxicity for instance blood urea nitrogen (BUN), creatinine, total protein, and albumin (P < 0.01, when compared with TAC treated group). Also, it significantly restored the increase activities of TBARS, protein carbonyl (PC) (P < 0.001, when compared to healthy control group) and decreased activities of nonprotein thiol (NPSH) levels, Mn-superoxide dismutase (Mn-SOD) and glutathione peroxidase (GPx) antioxidants of mitochondria. The nephroprotective efficacy of the OB leaves extract was further evident by histopathological analysis together with the PCNA-ir and Bcl2. The upshot of the present study revealed that the OB possessed significant antioxidant and nephroprotective activity and had a preventive effect on the biochemical alterations and histological changes in TAC-treated mice. Keywords: Tacrolimus, Nephrotoxicity, PCNA, Bcl-2, Ocimum basilicu

The Hdj-2/Hsc70 chaperone pair facilitates early steps in CFTR biogenesis.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride ion channel constructed from two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBD) and a regulatory (R) domain. The NBDs and R-domain are cytosolic and how they are assembled with the MSDs to achieve the native CFTR structure is not clear. Human DnaJ 2 (Hdj-2) is a co-chaperone of heat shock cognate 70 (Hsc70) which is localized to the cytosolic face of the ER. Whether Hdj-2 directs Hsc70 to facilitate the assembly of cytosolic regions on CFTR was investigated. We report that immature ER forms of CFTR and DeltaF508 CFTR can be isolated in complexes with Hdj-2 and Hsc70. The DeltaF508 mutation is localized in NBD1 and causes the CFTR to misfold. Levels of complex formation between DeltaF508 CFTR and Hdj-2/Hsp70 were approximately 2-fold higher than those with CFTR. The earliest stage at which Hdj-2/Hsc70 could bind CFTR translation intermediates coincided with the expression of NBD1 in the cytosol. Interestingly, complex formation between Hdj-2 and nascent CFTR was greatly reduced after expression of the R-domain. In experiments with purified components, Hdj-2 and Hsc70 acted synergistically to suppress NBD1 aggregation. Collectively, these data suggest that Hdj-2 and Hsc70 facilitate early steps in CFTR assembly. A putative step in the CFTR folding pathway catalyzed by Hdj-2/Hsc70 is the formation of an intramolecular NBD1-R-domain complex. Whether this step is defective in the biogenesis of DeltaF508 CFTR will be discussed

Preliminary seismic hazard assessment for Los Angeles, Ventura, and Orange Counties, California, affected by the 17 January 1994 Northridge earthquake

The seismic ground motion hazard is assessed for a 10% probability of exceedance in 50 years for the three counties (Los Angeles, Ventura, and Orange) impacted by the 1994 Northridge earthquake (Mw 6.7). The earthquake source model of the Southern California Earthquake Center has been modified with additional slip-rate information for mapped faults and blind thrusts and incorporated into seismic hazard maps that will be used for making regional hazard and risk mitigation decisions by state and local government agencies. Peak horizontal ground acceleration (pga) and 5% damped spectral acceleration (SA) (0.3 and 1 sec) were calculated with three equally weighted attenuation relationships of Boore et al. (1993), Campbell and Bozorgnia (1994), and Sadigh (written comm., 1994). The results of this assessment indicate high hazard over the entire tri-county area with ground motions exceeding 0.4 g (pga), 1.0 g (0.3-sec SA), and 0.5 g (1-sec SA) nearly everywhere. A Monte Carlo uncertainty analysis is described for two sites located in Los Angeles and Northridge. This analysis yields 95% confidence limits for peak ground acceleration at the two sites that range between ±0.1 and ±0.2 g. Our calculations indicate that the uncertainty in the magnitude-rupture length relations, magnitude distribution, moment-magnitude relation, attenuation relation, and slip-rate contribute most to the hazard uncertainty at these sites and that the highest uncertainties in the mapped ground motion are associated with the strongest anticipated ground motions