Effects of adenosine triphosphate, Lacidipine, and Benidipine on 5-fluorouracil-induced kidney damage in rats.

OBJECTIVE: In the present study, the protective effects of adenosine triphosphate (ATP), Benidipine, and Lacidipine on potential kidney damage induced by 5-fluorouracil (5-FU) were investigated in rats. MATERIALS AND METHODS: Totally 48 rats were divided into 8 groups: healthy (HG), 5-FU (FUG), ATP+5-FU (AFU), Benidipine+5-FU (BFU), Lacidipine+5-FU (LFU), ATP+Benidipine+5-FU (ABFU), ATP+Lacidipine+5-FU (ALFU) and Benidipine+Lacidipine+5-FU (BLFU). In a 10-day period, ATP (4 mg/kg) was administered intraperitoneally, and Benidipine (4 mg/kg) and Lacidipine (4 mg/kg) were administered orally once a day. On days 1, 3, and 5, 5-FU (100 mg/kg) was administered intraperitoneally one hour after the drug was administered. Afterward, the rats were euthanized, and kidney tissues were removed. An analysis of malondialdehyde, total glutathione, superoxide dismutase, and catalase was performed on tissues, as well as a histopathological examination. A creatinine and blood urea nitrogen analysis were performed on blood samples. RESULTS: It was revealed that 5-FU decreased the amount of total glutathione, superoxide dismutase, and catalase activities in rat kidney tissues and increased malondialdehyde. Further, increased serum creatinine and blood urea nitrogen levels, as well as histopathological examination of kidney tissues, were found in the 5-FU group. ATP+Benidipine and ATP treatments were the most effective in preventing both biochemical and histopathological changes induced by 5-FU. A treatment with Benidipine improved biochemical and histopathologic data, but not to the same extent as a treatment with ATP+Benidipine and ATP. As a result of Lacidipine+ATP combination, 5-FU-induced biochemical changes in kidney tissue were partially inhibited, but the degree of histopathologic damage remained unchanged. Neither Benidipine+Lacidipine nor Lacidipine showed a protective effect on both biochemical changes and histopathologic damage. CONCLUSIONS: It may be possible to prevent nephrotoxicity by adding ATP + Benidipine or ATP to 5-FU treatment.

Effect of pycnogenol on ethanol-related oxidative retinal injury: an experimental study.

OBJECTIVE: We aimed at determining the protective effects of Pycnogenol on ethanol-induced retinotoxicity in an experimental model. MATERIALS AND METHODS: 30 male Wistar albino rats were randomly divided into three groups: an untreated healthy control (HC group), a group in which only ethanol was daily administered for six weeks (EtOH group), and a group in which ethanol + 40 mg/kg Pycnogenol was daily administered orally for six weeks (PEtOH group). The same volume (0.5 ml) of distilled water as solvent was applied in the same manner to the rats in the HC and EtOH groups. With the rats in the PEtOH and EtOH groups, 32% ethanol at a dose of 5 g/kg was administered by oral gavage one hour after the application of pycnogenol or distilled water. At the end of the experimental period, tissue samples were obtained for biochemical examination of malondialdehyde (MDA) and total glutathione (tGSH) levels, and afterwards, the eyes were removed for histopathological examination. RESULTS: Histopathological evaluations in the EtOH group showed significant destruction of retinal tissue with marked edema, decomposition and degeneration in layers, polymorphonuclear cell infiltration, dilatation and congestion in blood vessels. However, it was observed that MDA values increased and tGSH values decreased in the EtOH group. In the PEtOH group, MDA values decreased and GSH values increased. Again, degenerative changes were considerably less in this group. CONCLUSIONS: In the light of biochemical markers and histopathological evaluations, it was observed that ethanol exposure caused a significant degeneration in the retinal tissue. It was found that Pycnogenol administration significantly reduced the destructive effects seen histopathologically. Biochemical results also coincided with other findings. It was concluded that ethanol-induced rethytosis can be prevented to a large extent by Pycnogenol administration.

Single-cell analysis of endometriosis reveals a coordinated transcriptional programme driving immunotolerance and angiogenesis across eutopic and ectopic tissues.

Endometriosis is characterized by the growth of endometrial-like tissue outside the uterus. It affects many women during their reproductive age, causing years of pelvic pain and potential infertility. Its pathophysiology remains largely unknown, which limits early diagnosis and treatment. We characterized peritoneal and ovarian lesions at single-cell transcriptome resolution and compared them to matched eutopic endometrium, unaffected endometrium and organoids derived from these tissues, generating data on over 122,000 cells across 14 individuals. We spatially localized many of the cell types using imaging mass cytometry. We identify a perivascular mural cell specific to the peritoneal lesions, with dual roles in angiogenesis promotion and immune cell trafficking. We define an immunotolerant peritoneal niche, fundamental differences in eutopic endometrium and between lesion microenvironments and an unreported progenitor-like epithelial cell subpopulation. Altogether, this study provides a holistic view of the endometriosis microenvironment that represents a comprehensive cell atlas of the disease in individuals undergoing hormonal treatment, providing essential information for future therapeutics and diagnostics.

The protective effect of lycopene against oxidative kidney damage associated with combined use of isoniazid and rifampicin in rats.

It is known that the combined use of antibiotics, such as isoniazid and rifampicin, in the treatment of tuberculosis causes oxidative kidney damage. The aim of this study was to biochemically and histopathologically investigate the effect of lycopene on oxidative kidney damage due to the administration of isoniazid and rifampicin in albino Wistar male rats. Lycopene at a dose of 5 mg/kg was orally administered to lycopene+isoniazid+rifampicin (LIR) rats, and normal sunflower oil (0.5 mL) was orally administered to isoniazid+rifampicin (IR) and healthy control (HG) rats as vehicle by gavage. One hour after the administration of lycopene and vehicle, 50 mg/kg isoniazid and rifampicin were given orally to the LIR and IR groups. This procedure was performed once a day for 28 days. Rats were sacrificed by a high dose of anesthesia at the end of this period, and oxidant-antioxidant parameters were measured in the removed kidney tissues. Creatinine and blood urea nitrogen (BUN) levels were measured in blood samples, and kidney tissues were also evaluated histopathologically. The combined administration of isoniazid and rifampicin changed the oxidant-antioxidant balance in favor of oxidants, and it increased blood urea nitrogen and creatinine levels, which are indicators of kidney function. Co-administration of isoniazid and rifampicin also caused oxidative kidney damage. Lycopene biochemically and histopathologically decreased oxidative kidney damage induced by isoniazid and rifampicin administration. These results suggested that lycopene may be beneficial in the treatment of nephrotoxicity due to isoniazid and rifampicin administration.

The protective effect of lycopene against oxidative kidney damage associated with combined use of isoniazid and rifampicin in rats

It is known that the combined use of antibiotics, such as isoniazid and rifampicin, in the treatment of tuberculosis causes oxidative kidney damage. The aim of this study was to biochemically and histopathologically investigate the effect of lycopene on oxidative kidney damage due to the administration of isoniazid and rifampicin in albino Wistar male rats. Lycopene at a dose of 5 mg/kg was orally administered to lycopene+isoniazid+rifampicin (LIR) rats, and normal sunflower oil (0.5 mL) was orally administered to isoniazid+rifampicin (IR) and healthy control (HG) rats as vehicle by gavage. One hour after the administration of lycopene and vehicle, 50 mg/kg isoniazid and rifampicin were given orally to the LIR and IR groups. This procedure was performed once a day for 28 days. Rats were sacrificed by a high dose of anesthesia at the end of this period, and oxidant-antioxidant parameters were measured in the removed kidney tissues. Creatinine and blood urea nitrogen (BUN) levels were measured in blood samples, and kidney tissues were also evaluated histopathologically. The combined administration of isoniazid and rifampicin changed the oxidant-antioxidant balance in favor of oxidants, and it increased blood urea nitrogen and creatinine levels, which are indicators of kidney function. Co-administration of isoniazid and rifampicin also caused oxidative kidney damage. Lycopene biochemically and histopathologically decreased oxidative kidney damage induced by isoniazid and rifampicin administration. These results suggested that lycopene may be beneficial in the treatment of nephrotoxicity due to isoniazid and rifampicin administration.

Prevention of infertility induced by ovarian ischemia reperfusion injury by benidipine in rats: Biochemical, gene expression, histopathological and immunohistochemical evaluation.

INTRODUCTION: Benidipine has been reported to prevent the ischemia/reperfusion (I/R) damage in heart tissue and to suppress oxidant and proinflammatory cytokine production, increased by I/R. However, There was no information about the effects of benidipine on I/R injury in the ovary and the damage of I/R-induced infertility. OBJECTIVES: The aim of the study was to investigate the effects of benidipine on bilateral ovarian I/R injury and whether or not effective in the treatment of I/R-induced infertility in rats. METHOD: Forty-eight females, albino Wistar rats were randomly divided into 4 groups: IRC group (ovarian I/R group, n=12), IRB-2 group (ovarian I/R+2mg/kg benidipine group, n=12), IRB-4 group (ovarian I/R+4mg/kg benidipine group, n=12) and HG group (healthy group with sham operation, n=12). In IRB-2 and IRB-4 groups, two hours ischemia and two hours reperfusion was performed following orally benidipine administration. After this I/R procedure, 6 rats from each group performed bilateral overectomy. Ovarian levels of malondialdehyde (MDA) and total glutathione (tGSH), ovarian gene expressions of interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) and also apoptosis were evaluated. The other 6 rats from each group were put in together with six male rats in separated cages for 2 months in order to reproduce. During this period, rats which did not become pregnant were accepted as infertile. RESULTS: MDA levels, expressions of TNF-α and IL-1ß in IRC group were significantly higher than in the SGA group and tGSH was decreased. In total, 4mg/kg benidipine has better prevented ovaries from the increase of oxidants and proinflammatory cytokines, the decrease of antioxidants than 2mg/kg benedipine. In the histopathological examination hemorrhage, congestion, follicle degeneration, neutrophil infiltration and necrosis were seen in ovarian tissue of IRC group. Only dilated and congested blood vessels were found in the IRB-2 group. No histopathological finding was encountered in the IRB-4 group. I/R caused infertility in rats. In total, 4mg/kg benidipine prevented from infertility better than the dose of 2mg/kg benedipine. CONCLUSION: In total, 4mg/kg benidipine reduced I/R injury and I/R-related infertility more significantly compared to 2mg/kg benedipine in rat ovaries.

Comparison of preovulatory follicular concentrations of epidermal growth factor, insulin-like growth factor-I, and inhibins A and B in women undergoing assisted conception treatment with gonadotropin-releasing hormone (GnRH) agonists and GnRH antagonists.

Follicular fluid contents of 69 age-matched women undergoing ovarian stimulation with a GnRH agonist and a GnRH antagonist were collected during oocyte retrieval. The groups did not differ in baseline characteristics and in terms of assisted conception treatment outcome. Similarly, follicular fluid levels of epidermal growth factor, insulin-like growth factor, and inhibins A and B were found not to be different. Our results suggest that follicular development in regard to ovarian growth factor dynamics is not different in women undergoing ovarian stimulation with GnRH antagonists than in women using GnRH agonists.