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.

Protective effect of Coenzyme Q10 on oxidative ovarian and uterine damage induced by methotrexate in rats.

Methotrexate (MTX) has toxic effects on the uterus and ovaries via oxidative stress. Coenzyme Q10 (CoQ10) is an important component in electron transport in the mitochondria and an antioxidant in cellular metabolism through the inhibition of lipid peroxidation. The aim of this study was to investigate the preventive effects of CoQ10 on MTX-induced utero-ovarian damage and oxidative stress in rats.In this experimental study, 30 albino Wistar female rats were divided randomly into three groups. Once a day for a month, 10 mg/kg of CoQ10 was orally administered to the rats in the MTX+CoQ10 group, while the same volume of olive oil was administered orally to the other two groups. One hour thereafter, 20 mg/kg of MTX was injected intraperitoneally into the rats in the MTX and MTX+CoQ10 groups; the remaining group was the control. At the end of the month, biochemical and histopathologic examinations were performed on the extracted uteri and ovaries. In the uterine ovarian tissues of the animals in the MTX group, there was an increase in oxidative stress mediators and a decrease in antioxidant and anti-inflammatory mediators, but these trends were reversed in the MTX+CoQ10 group, demonstrating the antioxidant effects of CoQ10. MTX leads to oxidative stress-related ovarian and uterine injury, and CoQ10 may be useful for protecting ovarian and uterine tissue from such injury.

Protective effect of adenosine triphosphate against sunitinib-related skin damage in rats.

Cutaneous side effects associated with sunitinib use are a major problem in patients receiving cancer treatment. The aim of this study was to investigate the protective effect of adenosine triphosphate (ATP) against possible skin damage resulting from sunitinib use in rats. Thirty Albino Winstar rats were divided into the following three groups: healthy controls (HCs, n = 10), sunitinib (SUN, n = 10), and sunitinib + ATP (SAT, n = 10). ATP was injected intraperitoneally at a dose of 2 mg/kg. One hour subsequent to the administration of ATP and 0.9% NaCl, the SAT and SUN groups were orally administered a dose of 25 mg/kg sunitinib to the stomach. Macroscopic evaluation of the skin indicated lower levels of skin damage in the SAT group than in the SUN group. As an indicator of oxidative stress, malondialdehyde (MDA), total oxidant status (TOS), and oxidative stress index (OSI) levels were significantly higher in the SUN group than in the HC group, while total glutathione (tGSH) and total antioxidant status (TAS) levels were significantly lower. However, MDA, TOS, and OSI levels were significantly lower in the SAT group than in the SUN group, while tGSH and TAS levels were significantly higher. Histopathological examination revealed keratin plugs with edema, vasopathology, and inflammatory cell infiltration in the SUN group. The SAT group showed less necrotic epithelium, keratin plugs, edema, and vasopathology than the SUN group. ATP can be effective in preventing skin damage caused by sunitinib use by reducing oxidative stress.

The effect of adenosine triphosphate on sunitinib-induced cardiac injury in rats.

In this study, we aimed to show the effect of adenosine 5'-triphosphate (ATP) on sunitinib-induced cardiac injury in rats. The rats (n = 30) were divided equally into three groups as sunitinib group (SG), sunitinib plus ATP group (SAG), and healthy group (HG); 2 mg/kg ATP was injected intraperitoneally (ip) to the SAG group. Same volume normal saline as solvent was administered ip to the other two groups. After 1 h, 25 mg/kg sunitinib was applied orally via catheter to stomach in the SAG and SG groups. This procedure was repeated once daily for 5 weeks. At the end of this period, all animals were sacrificed and their cardiac tissue was removed. Malondialdehyde (MDA), total glutathione (tGSH), tumor necrosis factor α (TNF-α), and nuclear factor κB (NF-κB) levels in rats' cardiac tissues and troponin I (Tp-I) levels in rats' blood samples were evaluated. Histopathological analysis was also performed in cardiac tissues of the animals. MDA, TNF-α, NF-κB, and Tp-I levels were higher in the SG group compared to the SAG and HG groups (p < 0.001). tGSH levels of the SG group were lower than the SAG and HG groups (p < 0.001). The structure and morphology of cardiac muscle fibers and blood vessels were normal in the control group. In the SG group, obvious cardiac muscle tissue damage with dilated myofibers, locally atrophic myofibers, and congested blood vessels were observed. In the SAG group, marked amelioration in these findings was observed. We showed this for the first time that ATP administration exerts a protective effect against cardiac effects of sunitinib.

Aspartame induces angiogenesis in vitro and in vivo models.

Angiogenesis is the process of generating new blood vessels from preexisting vessels and is considered essential in many pathological conditions. The purpose of the present study is to evaluate the effect of aspartame on angiogenesis in vivo chick chorioallantoic membrane (CAM) and wound-healing models as well as in vitro 2,3-bis-2H-tetrazolium-5-carboxanilide (XTT) and tube formation assays. In CAM assay, aspartame increased angiogenesis in a concentration-dependent manner. Compared with the control group, aspartame has significantly increased vessel proliferation (p < 0.001). In addition, in vivo rat model of skin wound-healing study showed that aspartame group had better healing than control group, and this was statistically significant at p < 0.05. There was a slight proliferative effect of aspartame on human umbilical vein endothelial cells on XTT assay in vitro, but it was not statistically significant; and there was no antiangiogenic effect of aspartame on tube formation assay in vitro. These results provide evidence that aspartame induces angiogenesis in vitro and in vivo; so regular use may have undesirable effect on susceptible cases.

Endovesical leiomyoma of bladder: a case report.

Benign mesenchymal tumors cover 0,04-0,5% of all bladder tumors and their major part consists of leiomyomas. Having the smooth muscle tissue origin, these tumors can exhibit intramural, endovesical and extravesical localization in the bladder. Clinically, the irritative and obstructive symptoms, hematuria accompany endovesical leiomyomas. Along side being asymptomatic, intramural and extravesical leiomyomas can sometimes be characterized by mass formation, hematuria, and irritative symptoms, rarely by obstructive symptoms. In the diagnostic process histopathology is of great importance, especially in exclusion of radiologically and cystoscopically indistinguishable lesions. A case of endovesical leiomyoma of bladder in 49 year-old male patient admitted to the hospital with a complaint of hematuria and irritative symptoms is presented. Transurethral resection is performed for the patient with the purpose of treatment and diagnosis, and follow-up with ultrasonography was deemed appropriate once every three months. In the macroscopic examination of the material 4,0 cc of white-and-pink-colored, soft tissue fragments from 0,5 to 1,8 cm in diameter were observed. A well-vascularized tumor tissue composed of spindle cells with uniform and elongated nucleuses and normal urothelial epithelium with no specific features on its surface was observed in the microscopic examination. Recurrence wasn`t observed during 32-month follow-up. As bladder leiomyoma is a rare pathology, generally accepted follow-up scheme for this disease after the treatment isn't reported. For this reason, we did the follow-up of the patient in a minimally invasive way that doesn't comply with the EAU guidelines - ultrasonography of urinary tract was performed on the patient on quarterly basis. After the 32 month-follow-up, no recurrence was seen. As a result, the bladder leiomyoma is a rare, and it requires careful pathological examination. Due to the lack of knowledge about this tumor large scale of studies.