Molecular insights into the antioxidative and anti-inflammatory effects of P-coumaric acid against bisphenol A-induced testicular injury: In vivo and in silico studies.

This study investigated the protective effects of p-coumaric acid (PCA) against bisphenol A (BPA)-induced testicular toxicity in male rats. The rats were divided into control, BPA, BPA+PCA50, BPA+PCA100, and PCA100 groups. Following a 14-day treatment period, various analyses were conducted on epididymal sperm quality and testicular tissues. PCA exhibited dose-dependent cytoprotective, antioxidant, and anti-inflammatory effects, ameliorating the decline in sperm quality induced by BPA. The treatment elevated antioxidant enzyme activities (SOD, GPx, CAT) and restored redox homeostasis by increasing cellular glutathione (GSH) and reducing malondialdehyde (MDA) levels. PCA also mitigated BPA-induced proinflammatory responses while reinstating anti-inflammatory IL-10 levels. Apoptotic parameters (p53 and p38-MAPK) were normalized by PCA in BPA-treated testicular tissue. Immunohistochemical and immunofluorescent analyses confirmed the cytoprotective and anti-inflammatory effects of PCA, evidenced by the upregulation of HO-1, Bcl-2, and Nrf-2 and the downregulation of the proapoptotic gene Bax in BPA-induced testicular intoxication. PCA corrected the disturbance in male reproductive hormone levels and reinstated testosterone biosynthetic capacity after BPA-induced testicular insult. In silico analyses suggested PCA's potential modulation of the oxidative stress KEAP1/NRF2/ARE pathway, affirming BPA's inhibitory impact on P450scc. This study elucidates BPA's molecular disruption of testosterone biosynthesis and highlights PCA's therapeutic potential in mitigating BPA's adverse effects on testicular function, showcasing its cytoprotective, anti-inflammatory, and hormone-regulating properties. The integrated in vivo and in silico approach offers a comprehensive understanding of complex mechanisms, paving the way for future research in reproductive health and toxicology, and underscores the importance of employing BPA-free plastic wares in semen handling.

Investigation of the effect of hesperidin on some reproductive parameters in testicular toxicity induced by Bisphenol A.

Bisphenol A (BPA) is one of the chemicals that cause dysfunction and infertility in testicles. Therefore, it is crucial to develop effective treatments against this damage. In this study, the effects of Hesperidin (HESP), a flavonoid in testicular toxicity induced by BPA in rats, on oxidative stress, inflammation, apoptosis, histological damage, spermatogenesis, steroidogenic enzymes and reproductive hormones were investigated. Our study used 52 Sprague Dawley male rats weighing 250-300 g, and four experimental groups were formed. From the experimental groups, 1 ml of olive oil was administered to the control group, HESP at a dose of 50 mg/kg to the HESP group, BPA at a dose of 100 mg/kg to the BPA group, HESP at a dose of 50 mg/kg to the BPA + HESP group and 100 mg/kg BPA was administered intragastrically (ig) for 14 days. We determined that BPA administration causes apoptosis, histological damage, inflammation, oxidative stress and toxic effects on spermatogenesis and steroidogenic enzymes in testicles. We observed that the administration of HESP with BPA attenuated oxidative stress, inflammation and apoptosis resulting in therapeutic effects on both steroidogenic enzymes and spermatogenesis and reproductive hormones (FSH, LH and testosterone). Our findings from this study clearly showed that while HESP treatment alleviates oxidative damage, inflammation and apoptosis in testicles of rats treated with BPA, it has regulatory effects on steroidogenic enzymes, spermatogenesis and serum reproductive hormones.

Probiotic bacteria attenuates cisplatin-induced nephrotoxicity through modulation of oxidative stress, inflammation and apoptosis in rats

Objective: To investigate the effects of probiotic bacteria on cisplatin (CP)-induced nephrotoxicity. Methods: In the present study, 50 Sprague-Dawley rats were used and randomly divided into five groups including control, CP, probiotic bacteria treatment groups with different doses (0.5 and 1 mL) and only probiotic bacteria group. After CP and probiotic administration on seven days, rats sacrificed under anesthesia on the eighth day. The serum urea, creatinine, and blood urea nitrogen levels were analyzed. In renal tissue, malondialdehyde levels, superoxide dismutase and glutathione activity, interleukin-8, interleukin-1β and tumor necrosis factor-alpha levels were determined and histopathological and immunohistochemical changes were also examined. Results: According to results, urea, creatinine and blood urea nitrogen levels as well as kidney weights increased in CP group. Also, CP induced inflammation, oxidative stress, DNA damage and apoptosis in kidney tissue and caused histopathological changes. Administration of the high dose of probiotic bacteria could prevent these changes and damages. Conclusions: This study reveals that probiotic bacteria has protective effects on CP-induced renal damage in rats.

The protective effect of quercetin on cyclophosphamide-Induced lung toxicity in rats.

Cyclophosphamide (CYP) is an anticancer agent widely used in chemotherapy. It has been suggested that CYP causes toxicity in many organs, including the lungs and testes. Many studies have indicated that some antioxidants have possible protective effects against CYP's side effects. This study aimed to investigate the protective effect of quercetin (QUE) on CYP-induced lung toxicity in rats using histologic and biochemical methods. In the study, 50 male Sprague-Dawley rats weighing 220-250g were used. There were 4 experimental groups and 1 control group. Group I is the control group, which was given only intragastric (i.g.) solvent (corn oil) for 7days. Group II was given i.g. corn oil for 7days as a placebo, and a single dose of intraperitoneal (i.p.) CYP (200mg/kg) was given on day 7. Groups III and IV, respectively, were given QUE in doses of 50 and 100mg/kg, dissolved in corn oil, and administered i.g. for 7days. In addition, a single dose of CYP (200mg/kg, i.p.) was administered on the 7th day of study. In Group V, a 100mg/kg dose of QUE was given to rats i.g. for 7days. On the 8th day of the experiment, all groups of rats' blood and lung tissue samples were collected for analysis of oxidative stress parameters and histopathological examinations. In the biochemical result (although oxidative parameters were increased in favor of tissue damage) QUE administration revealed attenuated CYP toxicity in the rats 'lungs. In histologic analysis, QUE prevented the CYP-mediated tissue damage and the increase in mast-cell densities in the rats' lung tissues. The results of the present study have revealed that QUE provides a possible protective effect by inhibiting ROS and mast cell degranulation in induced lung damage.

Impact of Rho-Kinase Inhibitor Hydroxyfasudil in Protamine Sulphate Induced Cystitis Rat Bladder.

OBJECTIVES: The objective of the present study was to evaluate anti-inflammatory effects of hydroxyfasudil in a protamine sulfate (PS) induced cystitis rat model. Additionally, we investigated prevention of bladder overactivity (BO), and tissue damage in these experiments. METHODS: Animals were divided into four groups. In Groups 1 and 2, chemical induced cystitis model was created by administrating intravesical PS with PE50 catheter by the transurethral route. In Group 1, Rho-kinase inhibitor hydroxyfasudil was administered intaperitoneally, and in Group 2, subjects were administered a corresponding volume of saline in the same way. In Group 3, vehicle was administered intravesically and hydroxyfasudil was administrated intraperitoneally. Group 4 was a control Group, and the vehicle was administered intravesically and intraperitoneally. Micturition frequencies were recorded. Biochemical analyses were performed for oxidative stress, and pathological evaluations were investigated. In vitro contractions of bladder tissue strips were measured in tissue-bath. RESULTS: There were significantly lower Lipid peroxidase levels and higher levels of Glutathione in Group 1 than Group 2 (P = 0.016, P = 0.001, respectively). There was generally more inflammation in Group 2 than the other groups as determined by microscopy. There were significantly higher frequencies of micturition, lower volume, and mean voided maximum urine output after PS administration in Groups 1 and 2. In vitro contraction responses of bladder strips to potassium chloride and acetylcholine were statistically higher in Group 2 than Groups 1 and 3. CONCLUSIONS: Significant reduction of inflammation by affecting the anti-oxidant defense systems was provided by hydroxyfasudil. Decreased in vitro responses to contractions of bladder smooth muscle strips were obtained. Hydroxyfasudil may be a potential new therapeutic option for inflammation and BO, in rat bladder.

Spirulina platensis protects against gentamicin-induced nephrotoxicity in rats.

The present study aimed to investigate the protective effect of Spirulina platensis (SP) on gentamicin sulphate (GS)-induced changes in the levels of lipid peroxidation and endogenous antioxidants in the kidney of rats. Sprague-Dawley rats were treated in separate groups as follows for 7 consecutive days: control (C), gentamicin sulphate (100 mg/kg i.p.) (GS), Spirulina platensis (1000 mg/kg orally) (SP) and Spirulina platensis (1000 mg/kg orally) plus gentamicin sulphate (100 mg/kg i.p.) (SP + GS). The degree of protection was evaluated by determining the effects of Spirulina platensis on malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPX) and nitric oxide (NO), and plasma creatinine and urea levels were estimated in kidney homogenates to evaluate antioxidant activity, and the kidney was histologically examined as well. Spirulina platensis elicited significant nephroprotective activity by decreasing lipid peroxidation (MDA) and elevated the levels of GSH, SOD, GPX, NO, creatinine and urea. Furthermore, these biochemical observations were supplemented by histological examination of the rat kidneys. In conclusion, the present study indicates a very important role of reactive oxygen species (ROS) and the relation to renal dysfunction and point to the therapeutic potential of Spirulina platensis in gentamicin sulphate induced nephrotoxicity.

Investigation of the pharmacokinetics and determination of tramadol in rabbit plasma by a high-performance liquid chromatography-diode array detector method using liquid-liquid extraction.

An HPLC system using a new, simple and rapid liquid-liquid extraction and high-performance liquid chromatography-diode array detector method (HPLC-DAD) detection was validated to determine tramadol concentration in rabbit plasma. The method described was applied to a pharmacokinetic study of intravenous tramadol injections in rabbits. The extraction with ethylacetate yielded good response. The recovery of tramadol from plasma averaged 90.40%. Serial plasma samples were obtained prior to, during and after completion of the infusion for determination of tramadol concentrations. Tramadol concentrations were measured using reverse-phase high-performance liquid chromatography and pharmacokinetic application with intravenous tramadol in rabbits revealed that tramadol followed one-compartment open model. Maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC) for tramadol were 14.3 microg mL(-1) and 42.2 microg h mL(-1), respectively. The method developed was successfully applied to a simple, rapid, specific, sensitive and accurate HPLC method for investigation of the pharmacokinetics of tramadol in rabbit plasma.