Soy protein intake increased bone mineral density under nonenergy-deficiency conditions but decreased it under energy-deficiency conditions in young female rats.

Many young individuals attempt to lose too much weight because of a false body image, which induces low bone mineral density (BMD) resulting from energy restriction. In addition, a decrease in estrogen has been observed along with the decrease in BMD. Estrogen is responsible for maintaining bone mass, and soybeans contain high levels of isoflavones, which have estrogen-like effects. Thus, we hypothesized that soy protein prevents low BMD caused by energy deficiency in young female rats. The purpose of this study was to examine the effect of soy protein intake on bone loss by energy deficiency in young female rats. Female Sprague-Dawley rats (6 weeks old) were randomly divided into the following 4 experimental groups: ad libitum feeding and casein diet (AL-Cas); ad libitum feeding and soy diet (AL-Soy); 40% energy restriction and casein diet (ER-Cas); and 40% energy restriction and soy diet (ER-Soy). The experimental period was 10.5 weeks. The AL-soy group had significantly higher BMD of the femur than the AL-Cas group (AL-Cas = 156 ± 5 mg/cm2, AL-Soy = 165 ± 7 mg/cm2; P < .05). Meanwhile, the ER-Soy group had significantly lower BMD of the tibia, femur, and lumbar spine than the ER-Cas group (ER-Cas = 147 ± 7 mg/cm2, ER-Soy = 133 ± 10 mg/cm2; P < .01). These results show that compared with ad libitum control groups, soy protein resulted in higher BMD under nonenergy deficiency, but under energy-deficiency conditions, it resulted in lower BMD.

Taurine Deficiency in Tissues Aggravates Radiation-Induced Gastrointestinal Syndrome.

Ionizing radiation administered for cancer treatment or from nuclear plant accidents are two common causes of radiation exposure. Ionizing radiation exposure generates reactive oxygen species and free radicals, which cause oxidative stress. We previously reported that taurine contributes to the recovery from radiation-induced injuries, suggesting its potential as a radioprotector and radiation mitigator. However, the effect of taurine on radiation-induced gastrointestinal syndrome remains poorly understood. The aim of this study was to examine the effect of taurine tissue depletion on radiation-induced gastrointestinal syndrome. Mouse models of radiation-induced gastrointestinal syndrome were established in TauT+/+ and TauT-/- mice by whole-body X-irradiation. We examined the 30-day survival rate, as well as the crypt-villus structure and proliferation of proliferating cell nuclear antigen (PCNA) + cells in the small intestine. The survival rate of TauT-/- mice was significantly lower than that of TauT+/+ mice. The villi in the small intestine of TauT-/- mice were significantly shorter than those in TauT+/+ mice. Additionally, there were significantly fewer PCNA+ cells in TauT-/- mice than in TauT+/+ mice. These data demonstrate that taurine is a key regulator of crypt stem cells and plays an important regulatory role in intestinal cell survival, proliferation, and fate. Therefore, taurine may reduce radiation-induced gastrointestinal syndrome.

Taurine and Its Anticancer Functions: In Vivo and In Vitro Study.

Taurine (2-aminoethanesulfonic acid) is a natural amino acid that is found widely in all mammalian tissues. Several studies have demonstrated that taurine has anti-inflammatory, antioxidant, and hypoglycemic effects. Recently, taurine not only mitigates the side effects of chemotherapy in cancer but also possesses antitumor properties, including inhibiting cancer cell proliferation and inducing apoptosis in certain cancers by differential regulating proapoptotic and antiapoptotic proteins. Antitumor studies of taurine are still in their infancy, and the mechanism of its antitumor effect is not fully understood. In this regard, it is worthwhile to study the antitumor mechanism of taurine, which may provide clues to develop new synthetic therapeutic molecules. In this mini review, we summarize the main effects of taurine that have shown suppressing actions in the initiation and progression of cancers. The underlying molecular mechanism also suggested that taurine can be a potential clinical application in tumor therapy. In addition, with the in-depth study of different biological functions of taurine, we found that many systemic diseases are associated with taurine. In this review, the research progress of taurine's antitumor effect is briefly summarized including the in vivo and in vitro studies in our laboratory.

Characterization of Bone Tissue and Bone Morphology in Taurine Transporter Knockout Mice.

Taurine, a sulfur-containing amino acid, has been shown to protect against tissue damage. It is highly accumulated in bone cells, including osteoblasts, where it enhances bone tissue formation. The quality of bone is defined by its microarchitecture, accumulated microscopic damage, collagen quality, mineral crystal size, and turnover rate. In this study, the effects of taurine depletion on bone metabolism and bone quality were investigated in taurine transporter knockout (TauT-/-) mice. The bone volume and trabecular number of 20-month-old male TauT-/- and TauT+/+ mice were measured by micro-computed tomography, and bone tissues were observed using hematoxylin and eosin and immunohistochemical staining methods. In the TauT-/- mice, the bone area of the proximal region of the femur was significantly smaller than that in the TauT+/+ mice, and the bone volume and trabecular number of the femur neck were significantly lower. Although the bone mineral densities in the mid-diaphysis and proximal regions were lower in the TauT-/- mice, the difference was significant for the proximal region only. Moreover, taurine depletion decreased the mineral density and strength parameters in the cancellous bone. The results of this study suggest that taurine plays an important role in maintaining bone quality.

Low-carbohydrate, high-fat diet, and running exercise influence bone parameters in old mice.

We examined the effects and interactions of a low-carbohydrate, high-fat (LCHF) diet and voluntary running exercise on bone in older mice. Male 19-mo-old mice were divided into four groups by diet (control vs. LCHF) and exercise (sedentary vs. voluntary running). The control diet was 55% carbohydrate, 23% protein, and 22% fat, and the LCHF diet was 10% carbohydrate, 33% protein, and 57% fat as percentages of calories. The experiment ended when the mice reached 24 mo old. Statistical analysis was conducted using two-way analysis of variance with diet and exercise. The LCHF diet decreased bone mineral content (BMC), bone mineral density, bone volume fraction, and trabecular number. There was no significant interaction between diet and exercise on many bone parameters. However, there were significant diet and exercise interactions on lumbar BMC and tibial trabecular total tissue volume and average cortical thickness. The LCHF diet attenuated the benefit of running exercise on lumbar BMC and caused running to have a negative effect on tibial trabecular total tissue volume. Our study suggests that the LCHF diet impairs bone mass and some trabecular microstructure and reduces the benefit of exercise on lumbar BMC in old mice.NEW & NOTEWORTHY An LCHF diet is used in treatment and prevention of diseases or improving exercise performance. However, some studies have shown that an LCHF diet diminishes bone in young rodents. Our study demonstrates that an LCHF diet impairs bone mass and some trabecular microstructure in old mice, which are similar to the previous studies using young rodents. Moreover, our study shows that an LCHF diet reduces the benefit of exercise on lumbar BMC in old mice.

Effects of Vitamin E on the immune system and tumor growth during radiotherapy.

PURPOSE: The purpose of this study is to evaluate the effects of Vitamin E (VE) on the immune system and tumor growth during radiotherapy (RT) in mice model. METHODS: C57BL/6NCrSlc mice were randomly distributed in four groups (control, VE alone, RT alone, and VE + RT). In the VE and VE + RT groups, VE was administered in the diet at 500 mg/kg. Radiation was delivered at 2 Gy in a single fraction on the whole body or at 6 Gy in three fractions locally in the RT and VE + RT groups. Changes in leukocytes and T lymphocytes were counted and compared between the four groups. To evaluate the effects on tumor growth, Ehrlich carcinoma cells were injected into the thighs of mice, and tumor volumes and growth inhibition rates were compared. RESULTS: The number of leukocytes was increased in the VE group compared with that in the control group. The magnitude of leukocyte recovery after RT was also increased by VE. This change was affected largely by alterations in lymphocytes and monocytes rather than that in granulocytes. Both CD4+ and CD8+ T lymphocytes were positively affected by VE. The tumor growth was inhibited not only by RT but also by VE alone. If RT was delivered with VE, tumor growth was markedly inhibited. CONCLUSION: VE could increase the number of leukocytes, primarily lymphocytes, even after RT was delivered. VE also inhibited the tumor growth in addition to RT. Thus, VE may be a useful radioprotective supplement in radiotherapy without inducing tumor growth.

Nordic Walking Increases Distal Radius Bone Mineral Content in Young Women.

Unlike the lumbar spine and femur, the radius does not bear a gravitational mechanical compression load during daily activities. The distal radius is a common fracture site, but few studies have addressed the effects of exercise on fracture risk. The aim of this study was to determine the effects of the pole push-off movement of Nordic walking (NW) on the bone mineral content (BMC) and areal bone mineral density (aBMD) of the distal radius and the muscle cross-sectional area (CSA) at the mid-humeral and mid-femoral levels. The participants were allocated to two groups: an NW group and a control group. The NW group walked at least 30 min with NW poles three times a week for six months. There were no significant changes in muscle CSA at the mid-humeral or mid-femoral levels between or within groups. There were also no significant changes in BMC or aBMD at 1/3 and 1/6 of the distance from the distal end of the radius in either group. However, the BMC and aBMD at 1/10 of the distance from the distal end of the radius were significantly increased by NW. The NW pole push-off movement provided effective loading to increase the osteogenic response in the ultra-distal radius. The ground reaction forces transmitted through the poles to the radius stimulated bone formation, particularly in the ultra-distal radius.

Protective Effects of Taurine on the Radiation Exposure Induced Cellular Damages in the Mouse Intestine.

There has been a growing interest in radiation effects as a result of the Fukushima nuclear power plant accident in 2011. Exposure to ionizing radiation causes oxidizing events to different organs such as the bone marrow, intestine, and kidney, which can result in radiation-induced injuries. Taurine (2-aminoethanesulfonic acid) is a sulfur-containing amino acid possessing several important physiological functions, including membrane stabilization, anti-oxidative activity, anti-inflammatory effects and modulation of intracellular calcium levels. Taurine appears to be an attractive candidate for use as a radioprotector and as a radiation mitigator, but its protection mechanism against radiation-induced cell damage is still unclear until now. In this review we describe some of the mechanisms explaining the radioprotective/mitigating effects of taurine on radiation-induced cellular damage and our recent findings on this subject.

The Potential Effects of Taurine in Mitigation of Radiation Nephropathy.

Taurine (2-aminoethanesulfonic acid) is a sulfur-containing organic acid possessing several important effects, including antioxidant and anti-inflammatory ones. Exposure to ionizing radiation generates free radicals and reactive oxygen species (ROS) in irradiated cells, and free radical generation leads to oxidative stress. It is known that radiation nephropathy includes an inflammation-based process in which ROS and cytokines are responsible. Different doses of explored radiation can cause apoptosis, inflammation and a profound oxidative stress in kidneys. Oxidative stress is involved in renal injury after exposure to both ionizing radiation and inflammation. In this review, we describe the protective effect of taurine against several kidney diseases and the potential effects of taurine in the mitigation of radiation nephropathy. We also report that X-irradiation decreased the expression of taurine and TauT in the kidney. Taurine administration suppressed the decrease in the expression of taurine and TauT in the kidney after radiation exposure. Taurine might contribute to the mitigation of kidney injury induced by radiation.

Plant Enzymes Decrease Prostate Cancer Cell Numbers and Increase TNF-α In Vivo: A Possible Role in Immunostimulatory Activity.

Increased caloric intake and Westernized dietary choices may be contributing toward a recent rising trend of incidences of chronic lifestyle-related diseases. In this study, we evaluated the anticancer properties of Plant Enzyme Validux (PEV) using a mouse model. Five-week-old male C3H mice were randomly distributed into four experimental groups: Control, PEV only, 6Gy irradiation only, and PEV + 6Gy. PEV was orally administered daily at 500 mg/kg for 14 days prior to three rounds of 2Gy irradiation. We focused on the anticancer action and immunostimulatory effects of PEV with and without irradiation. Oncogene suppression was observed after PEV treatment as was an increase in TNF-α, suggesting an antitumor effect. PEV administration also appeared to reduce oxidative stress as evidenced by a decrease in lipid peroxidation. In addition, PEV confirmed radioprotective effect by radical blocking ability by radiation irradiation. Immunological responses to PEV administration were evidenced by an increase in number of total white blood cells and T lymphocytes. Immunotherapy is drawing more and more attention as a treatment for prostate cancer, suggesting that there will be a need for the identification of specific targets for prostate cancer and for more basic research on the genetic aspects of immunotherapy. Thus, PEV may be of use as a radioprotective supplement during radiotherapy for tumor treatment.

Jump Exercise and Food Restriction on Bone Parameters in Young Female Rats.

We examined the effect of jump exercise on bone parameters in young female rats under food restriction. Seven-week-old female rats were divided into four groups: a sedentary and ad libitum feeding group (n = 10), a jump exercise and ad libitum feeding group (n = 9), a sedentary and 30% food restriction group (n = 9), and a jump exercise and 30% food restriction group (n = 10). The jump groups jumped 20 times/day, 5 times/week. The experiment lasted for 13 weeks. There were no interactions of jump exercise and food restriction on bone. Jump exercise under food restriction conditions induced higher bone strength, bone mineral content, bone area, bone mineral density (BMD), and cortical bone volume in young female rats, similar to rats under ad libitum feeding conditions. Bone strength parameters were not significantly different between ad libitum intake and food restriction with jump exercise training; however, BMD, bone size, and bone mass in the food restriction groups did not reach the levels of those in the ad libitum conditions group with jump exercise training. Neither jump exercise nor food restriction had a significant effect on serum estradiol or IGF-1. Our study reveals jump exercise attenuates loss of biomechanical properties and some bone sites with food restriction in young female rats.

Cellular and Molecular Level Mechanisms against Electrochemical Cancer Therapy.

Electrochemical treatment (ECT) is a promising new way to induce tumor regression by flowing direct current into the cancer tissue. ECT was applied to different kinds of tumors in clinical studies and showed good results. In addition, basic research has almost not been done in the field of evaluation of efficacy, dose-response, and cytotoxicity. Therefore, the objective is to study the cellular mechanism in the antitumor effect of ECT and to contribute data of basic research of ECT. In the cell-level study, tumor cells (Sarcoma-180, Scc-7, Ehrlich Carcinoma) were studied using ICR mice and C3H mice. In the study group, pH values of control, 10mA × 150secs, 10mA × 300secs, and 10mA × 600secs groups were measured five times each. In histological level studies, ECT was performed on tumors inoculated on the upper part of the right foot of C3H mice. In each group, mice were sacrificed by cervical dislocation 6, 12, and 24 hrs after ECT treatment, and tumors were removed. The excised tumor was fixed in tissue with 10% formalin, and HE staining and apoptosis antibody staining were carried out from the obtained tissue section and observation. In the study at the cellular level, statistically significant differences were observed in all ECT groups in Sarcoma in the tumor growth measurement study compared with the control group. Statistically significant differences were also observed in Scc-7 in all ECT groups compared to the control group. In the intratumoral pH measurement study, there was a statistically significant difference between the anode and the cathode in each group compared to the control group. In the examination at the histological level, microscopic observation of a slide stained with apoptosis antibody with a magnification of 400 times showed that 6hrs after ECT it was stronger and then decreased. By performing ECT, a weak current flows in the living body. As a result, changes in tissue pH, generation of gas, etc. occur. In this study, it was also confirmed that the intratumor pH value becomes strongly acidic on the anode side and strongly alkaline on the cathode side. In addition, this study confirmed the occurrence of gas during treatment of ECT. Changes in the pH and the like cause changes in the environment in the cell, denaturation of proteins, apoptosis, and necrosis. In this study, a significant increase in apoptosis was confirmed in each ECT group compared to the control group. Treatment effects by ECT were also observed in tumor growth measurement studies and tumor weight measurement studies. From these research results, ECT is considered to be effective as a tumor treatment method.

Characteristics of bone strength and metabolism in type 2 diabetic model Tsumura, Suzuki, Obese Diabetes mice.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by hyperglycemia, hyperinsulinemia, and complications such as obesity and osteoporosis. The Tsumura, Suzuki, Obese Diabetes (TSOD) mouse is an animal model of spontaneous obese T2DM. However, bone metabolism in TSOD mice is yet to be investigated. The objective of the present study was to investigate the effects of T2DM on bone mass, metabolism, microstructure, and strength in TSOD mice. METHODS: We determined the following parameters in TSOD mice and Tsumura, Suzuki, Non-obesity (TSNO) mice (as controls): serum glucose levels; serum insulin levels; bone mass; bone microstructure; bone metabolic markers; and bone strength. We also performed the oral glucose tolerance test and examined histological sections of the femur. We compared these data between both groups at pre-diabetic (10 weeks) and established (20 weeks) diabetic conditions. RESULTS: Bone strength, such as extrinsic mechanical properties, increased with age in the TSOD mice and intrinsic material properties decreased at both 10 weeks and 20 weeks. Bone resorption marker levels in TSOD mice were significantly higher than those in the control mice at both ages, but there was no significant difference in bone formation markers between the groups. Bone mass in TSOD mice was lower than that in controls at both ages. The trabecular bone volume at the femoral greater trochanter increased with age in the TSOD mice. The femoral mid-diaphysis in TSOD mice was more slender and thicker than that in TSNO mice at both ages. CONCLUSIONS: Bone mass of the femur was lower in TSOD mice than in TSNO mice because hyperinsulinemia during pre-diabetic and established diabetic conditions enhanced bone resorption due to high bone turnover. In addition, our data suggest that the bone mass of the femur was significantly reduced as a result of chronic hyperglycemia during established diabetic conditions in TSOD mice. We suggest that bone strength in the femur deteriorated due to the reduction of bone mass and because the femoral mid-diaphysis was more slender in TSOD mice.

Characteristics of Bone Strength and Metabolism in Type 2 Diabetic Model Nagoya Shibata Yasuda Mice.

We evaluated the suitability of Nagoya Shibata Yasuda (NSY) mice as an animal model for examining the influence of a glucose metabolism disorder on bone integrity, using Institute of Cancer Research (ICR) mice as controls. We selected six NSY and ICR mice each that were matched for weight, and measured serum glucose levels, serum insulin levels, and conducted an oral glucose tolerance test. Histological sections of the femurs of both mouse lines were prepared, and the bone strength, mass, and microstructure of the femur were compared, along with bone metabolism. Serum glucose levels were significantly higher in the NSY mice than in the control mice, but body weight and serum insulin levels did not differ between the groups. Bone mass, microstructure, and strength of the femur, and bone metabolism were lower in the NSY mice than in the control mice. In the cortical bone of the femur in the NSY mice, several parts were not stained with eosin, demonstrating a strong negative correlation between serum glucose levels and bone mineral density; however, there was a negative correlation between serum glucose levels and bone metabolic markers. The bone turnover rate in the NSY mice was decreased by hyperglycemia, resulting in a thinner and shorter femur, reduced cortical and trabecular areas, and lower bone mass compared to those of the control mice. Collectively, these results suggest deteriorated bone strength of the femur in NSY mice, serving as a useful model for studying the link between glucose metabolism and bone integrity.

[Rapid Decision of ESBL from Blood Culture Positive Bottles (Using MALDI-TOF MS and Sysmex UF-5000)].

In recent years, the appearance of MALDI-TOF MS made it possible to identify bacterial species in a short time. However, the sensitivity test has not largely shortened the time. When ESBL is suspected by routine examination, we speculate that there are many institutions conducting the inspection method conforming to the CLSI inspection procedure. When carrying out bacteria identification, susceptibility test and ESBL confirmation test from blood culture-positive specimens, the expected examination days are required for about 3 to 4 days, which is not quick. We report on bacterial species identification by MALDI-TOF MS from blood culture positive specimen bottle and ESBL rapid decision with fully automated urine analyzer.

Pharmaceutical Production of Anti-tumor and Immune-potentiating Enterococcus faecalis-2001 ß-glucans: Enhanced Activity of Macrophage and Lymphocytes in Tumor-implanted Mice.

BACKGROUND: Enterococcus faecalis 2001 is a probiotic lactic acid bacterium and has been used as a biological response modifier (BRM). From physiological limitation of bacterial preservation in storage and safety, the live E. faecalis 2001 has been heat-treated and the BRM components containing high level of ß-glucan, named EF-2001, were prepared. METHOD: The heat-treated EF-2001 has been examined for the antioxidative potential for radical scavenging and anti-tumor activities as well as immune-enhancing response in mice. Lymphocyte versus polymorphonuclear leukocyte ratio was increased in mice upon treatment with EF-2001. The number of lymphocytes was increased in the EF-2001-treated group. In the mice bearing two different Ehrlich solid and Sarcoma-180 carcinomas, the treatment with EF-2001 resulted in anti-tumor action. Tumor-suppressive capacity upon treatment with EF-2001 was significantly increased compared to normal controls. RESULTS: During the time interval administration of 5 weeks between the priming and secondary administration of EF-2001, the expression and production levels of TNF-α were also observed in the EF- 2001-administered mice. Additionally, anti-tumor activity examined with the intravenous administration of EF 2001 with a 34 times interval was also observed, as the growth of Sarcoma180 cells was clearly inhibited by the EF-2001. CONCLUSION: From the results, it was suggested that the immune response is enhanced due to antioxidative activity caused by the EF-2001 and anti-tumor activity by NK cells and TNF-α.

Does a Treadmill Running Exercise Contribute to Preventing Deterioration of Bone Mineral Density and Bone Quality of the Femur in KK-Ay Mice, a Type 2 Diabetic Animal Model?

Although it has been recently shown that type 2 diabetics have an increased risk of hip fracture, the effects of exercise therapy to prevent this have not been clarified. We examined whether a treadmill running exercise contributes to the bone mineral density (BMD) and bone microarchitecture of the femur and what kind of exercise intensity and duration are optimum in type 2 diabetes mellitus using KK-Ay diabetic mice. The mice were divided into two running groups, one fast speed and short duration (FS), the other slow speed and long duration (SL), and a group of controls with no running (CO). The running exercise was started when the mice were 8 weeks of age, and continued once a day 5 days per week for 10 weeks. Ten weeks after the start of the running exercise, the BMD of the proximal region and mid-diaphysis in the SL were significantly higher in comparison with that in the CO, whereas there was no difference in bone microarchitecture among the three groups. Blood glucose, insulin levels, and visceral fat contents in the SL were significantly lower than those in the CO and FS. Bone resorption protein and C-reactive protein levels in the SL were significantly lower than those in the CO. These results suggest that slow, long duration loading is better for both bone and glycemic control than fast, short duration loading in type 2 diabetes.

[MALDI-TOF MS Comparison of Blood Culture Positive Bottle Pretreatment Kit].

Identification of bacteria of sepsis or bacteremia is a useful result for treatment policy. In recent years, bacterial identification has become possible from blood culture bottles by MALDI‒TOF, but it is not as accurate as bacterial identification from agar colonies. Blood culture pretreatment kit (MALDI Sepcityper Kit) is currently on sale from Bruker. However, the current situation has not reached good accuracy. This time, a new blood culture pretreatment kit appeared, so I studied. Up to now, the blood culture pretreatment kit was only MALDI Sepcityper Kit using enzyme digestion method. Rapid BAC pro (Nittobo) is a pretreatment kit using nanomaterials. This time, comparison examination (total number 40 samples) was done. Among them, 33 specimens were identified by MALDI Sepcityper Kit. There were 21 specimens that could be identified by rapid BAC pro. In this study, rapid BAC pro did not show superior results over MALDI Sepcityper Kit.

Taurine Administration Mitigates Cisplatin Induced Acute Nephrotoxicity by Decreasing DNA Damage and Inflammation: An Immunocytochemical Study.

Cisplatin (CDDP) is one of the most effective chemotherapeutic agent used in the treatment of many kind of solid tumors. Its primary side effect is nephrotoxicity. The aim of this study to investigate the effects of taurine on cisplatin-induced acute nephrotoxicity. A single intraperitoneal injection of CDDP (15 mg/kg, or 25 mg/kg) deteriorated the kidney functions as reflected by histopathological changes. Histopathological changes were observed in all cisplatin groups. In the cisplatin group, oxidative stress was evident in the cisplatin group by observing an increase in 8-OHdG expression, an indicator of oxidative DNA damage. CDDP also resulted to an increase in CD68 expression in the renal tissues of CDDP groups. Taurine transporter (TauT) was down-regulated, and p53 was up-regulated in renal tissues as indicated by immunohistochemical analysis. Administration with taurine prior to a cisplatin injection was able to protect against deterioration of kidney function, to abrogate the decline in anti-oxidants and to suppress the increase in DNA damage. Moreover, taurine inhibited p53 activation and improved the pathological changes induced by cisplatin. This study demonstrates the protective effects of taurine in attenuating the expression of pro-inflammatory mediators and in improving antioxidant capacity in the kidney of cisplatin-injected rats. Thus, taurine could be a beneficial dietary supplement to attenuate cisplatin induced nephrotoxicity.

Effect of Taurine on iNOS-Mediated DNA Damage in Drug-Induced Renal Injury.

Owing to an outstanding wide antitumor spectrum and excellent anti-tumor effect cisplatin has been used in chemotherapy for malignant tumor. However, cisplatin has strong side effects such as renal injury. Taurine has been found to protect against inflammatory tissue damage in a variety of experimental models. The aim of the present study was to investigate the effect of taurine against iNOS dependent DNA damage in cisplatin-induced renal injury in rats. With the help of a rat model of drug-induced kidney damage, we have assessed the nephrotoxic effects of different doses of cisplatin in the presence and absence of taurine. Immunohistochemical methods were used to examine the distribution of arginine, iNOS, citrulline and 8-nitroguanine in renal tissue. The expression levels of citrulline, iNOS, and 8-nitroguanine immunoreactivities were found to increase as a function of the dose of cisplatin used, and to decrease in the presence of taurine. The expression level of arginine immunoreactivity was reduced as a function of the dose of cisplatin used. On the other hand, iNOS, 8-nitroguanine and citrulline immunohistochemical staining showed an intense immunoreactivity in the renal tubule of cisplatin-treated animals; and arginine immunoreactivity was localized in the renal tubule of taurine-treated animals. We also confirmed the decrease of citrulline and iNOS expression in the renal tubule after taurine administration as well as the expression level of 8-nitroguanine, a nitrative stress marker in the same animals. The present results support the concept that taurine may have a protective role in the formation of cisplatin-related DNA lesions arising through iNOS-mediated nitrative stress.