Effects of moderate intensity training and lithium on spatial learning and memory in a rat model: The role of SIRT3 and PGC1-α expression levels and brain-derived neurotropic factor.

In this study we investigated the potential synergistic effects of moderate interval training (MIT) and lithium on spatial learning and memory. Forty-two male Wistar males were classified into six groups including I: Control, II: 10 mg/kg/day IP lithium (Li10), III: MIT, IV: Li10 + MIT, V: 40 mg/kg/day IP lithium (Li40), and VI: Li40 + MIT. Then, the rats underwent Morris Water Maze (MWM) test to assess their spatial memory and learning ability. Brain-derived neurotrophic factor (BDNF) density was measured by enzyme-linked immunosorbent assay (ELISA), and the expression of PGC1 and SIRT3 were assessed via qRT-PCR. The results show that MIT improves both memory and spatial learning; but lithium alone, does not cause this. Additionally, those exposed to a combination of exercise and lithium also had improved spatial learning and memory. Finally, we observed a positive role of BDNF protein, and PGC1 gene on the effects of exercise and lithium.

Anesthesia and analgesia for common research models of adult mice.

Anesthesia and analgesia are major components of many interventional studies on laboratory animals. However, various studies have shown improper reporting or use of anesthetics/analgesics in research proposals and published articles. In many cases, it seems "anesthesia" and "analgesia" are used interchangeably, while they are referring to two different concepts. Not only this is an unethical practice, but also it may be one of the reasons for the proven suboptimal quality of many animal researches. This is a widespread problem among investigations on various species of animals. However, it could be imagined that it may be more prevalent for the most common species of laboratory animals, such as the laboratory mice. In this review, proper anesthetic/analgesic methods for routine procedures on laboratory mice are discussed. We considered the available literature and critically reviewed their anesthetic/analgesic methods. Detailed dosing and pharmacological information for the relevant drugs are provided and some of the drugs' side effects are discussed. This paper provides the necessary data for an informed choice of anesthetic/analgesic methods in some routine procedures on laboratory mice.

Angiotensin-Converting Enzyme 2 Roles in the Pathogenesis of COVID-19.

The new pandemic Coronavirus Disease 2019 (COVID-19) causes a wide range of clinical consequences, from asymptomatic infection to acute respiratory failure, and it is very heterogeneous. The renin-angiotensin system (RAS) is well recognized as a key regulating system in circulatory homeostasis that plays prominent roles in pathophysiological processes in abnormal activation, for instance, renal and cardiovascular diseases, obesity, and stroke. Angiotensin-converting enzyme 2(ACE2) is a component of the RAS system. However, unlike the ACE, its activity is not inhibited by the ACE inhibitors. The major product of ACE2 is Ang1-7, known as a vasodilator peptide and part of the depressant arm of the RAS. There are two forms of ACE2; Transmembrane ACE2 and soluble ACE2. Coronavirus is covered with some proteins in order to help viral attachment to the cell membrane ACE2 as a receptor and then fuse and enter the cells. ACE2 was expressed in the oral cavity, salivary glands of the mouth, esophagus, myocardial cells, kidney, and enterocytes, along with all the respiratory tract, intestine, and blood vessels. In this article, the renin- angiotensin system and its components have been explained. Moreover, the organs involved in COVID-19 disease, and the possible causes of damage to these organs have also been discussed. The probable mechanism of using ACE2 in viral attachment and the probable treatment processes will also be reviewed based on the surface proteins of the virus and ACE2. In addition, we briefly discuss anti-angiotensin drugs and why patients with chronic diseases are more susceptible to COVID-19 infection and show worse progression.

The Effect of Influenza Vaccination on COVID-19 Morbidity, Severity and Mortality: Systematic Review and Meta-Analysis.

Coronavirus disease 2019 (COVID-19) pandemic is rapidly developing worldwide with a high mortality rate. In this meta-analysis study, the effect of influenza vaccination on the prevention of COVID-19 and its consequences in patients were investigated. The systematic search for this study was performed from November 2019 to 25 November 2020, in the databases of Medline, PubMed, Scopus, Web of Science, Embase, Ebsco, Cochrane and medRxiv. Search terms used included COVID-19, coronavirus, SARS-CoV-2, covid, influenza, flu, grippe and vaccine. The present study examined the association between influenza vaccination and COVID-19 including COVID-19 infection, mortality, hospitalisation and intensive care unit (ICU) admission. Finally, the pooled estimates for different outcomes were calculated by the software for statistics and data science (STATA) version 15 and I2 was used to determine the heterogeneity. By analysing the data of articles, the pooled estimates of these data indicated that influenza vaccination could lower probability of COVID-19 infection up to 24% (OR = 0.77; 95% CI: 0.65, 0.91), of death up to 32% (OR = 0.68; 95% CI: 0.42, 1.11), of the hospitalisation up to 25% (OR = 0.75; 95% CI: 0.46; 1.23) and of admission to ICU up to 29% (OR = 0.71; 95% CI: 0.40, 1.27). Influenza vaccination can help decrease the COVID-19 infection and reduce hospitalisation and the need for ICU and mortality rates.

Eugenol Administration Improves Liver Damage Induced by a Fructose-Rich Diet.

BACKGROUNDS: The prevalence of metabolic syndrome (MetS) is increasing in developing countries that affects the liver in a variety of ways. This study was designed to investigate the protective role of eugenol on liver damage caused by fructose-induced MetS. MATERIALS AND METHODS: Thirty male Wistar rats were randomly divided into five groups: 1: tap water (control), 2: fructose, 3: fructose + eugenol solvent, 4: fructose + eugenol 50 mg/kg, and 5: fructose + eugenol 100 mg/kg. At the end of the experiment, blood samples were taken for measurement fast blood glucose (FBG), serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), low-density lipoprotein, high-density lipoprotein, cholesterol, and triglyceride. RESULTS: FBG significantly increased in Group 2 compared to Group 1 (P < 0.001); however, it significantly decreased in Groups 4 and 5 compared to Group 2 (P < 0.05). SGOT and SGPT levels significantly increased in Group 2 compared to the control group (P < 0.001). However, SGOT and SGPT levels significantly decreased in Groups 4 and 5. Malondialdehyde (MDA) and liver tissue damage score (LTDS) significantly increased in Group 2 compared with the control group (P < 0.01), whereas MDA and LTDS decreased in Groups 4 and 5 compared to Group 2 (P < 0.05). CONCLUSION: Eugenol may ameliorate liver damage in a rat model of fructose-induced MetS, and these protective effects may in part be mediated by improving antioxidant status and reducing oxidative stress and lipid peroxidation. It may also reduce hepatic inflammation and fat accumulation as well as fibrosis of liver cells.

Gastrointestinal and renal complications in SARS-CoV-2-infected patients: Role of immune system.

The recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease has been accompanied by various gastrointestinal (GI) and renal manifestations in significant portion of infected patients. Beside studies on the respiratory complications of coronavirus infection, understanding the essential immunological processes underlying the different clinical manifestations of virus infection is crucial for the identification and development of effective therapies. In addition to the respiratory tract, the digestive and urinary systems are the major sources of virus transmission. Thus, knowledge about the invasion mechanisms of SARS-CoV-2 in these systems and the immune system responses is important for implementing the infection prevention strategies. This article presents an overview of the gut and renal complications in SARS-CoV-2 infection. We focus on how SARS-CoV-2 interacts with the immune system and the consequent contribution of immune system, gut, and renal dysfunctions in the development of disease.

Simultaneous use of oxalate-degrading bacteria and herbal extract to reduce the urinary oxalate in a rat model: A new strategy.

OBJECTIVE: Urinary stones with oxalate composition can cause kidney failure. Recent findings evidenced that probiotics are effective in reducing oxalate absorption in these subjects based on their high colonic absorption levels at baseline. The purpose of this study was to evaluate the effect of the simultaneous use of oxalate-degrading bacteria, Urtica dioica and T. terrestris extract in reducing urinary oxalate. MATERIALS AND METHODS: Anti-urolithiatic activity of Urtica dioica and T. terrestris extract and pro-biotic by using ethylene glycol induced rat model. In this study, 4 strains of Lactobacillus and 2 strains of Bifidobacterium and also 2 strains of L. paracasei (that showed high power in oxalate degrading in culture media) were used. Male Wistar rats were divided into four groups (n=6). The rats of group-I received normal diet (positive control group) and groups-II (negative control group), III, IV rats received diet containing ethylene glycol (3%) for 30 days. Groups III rats re-ceived Urtica dioica and T. terrestris extract. Groups IV rats received extracts + probiotic for 30 days. FINDINGS: The results show that the use of herbal extracts (Urtica dioica and T. terrestris) redu-ced the level of urinary oxalate and other parameters of urine and serum. Also, the accumulation of calcium oxalate crystals in the kidney tissue was significantly reduced. CONCLUSION: Considering that the formation of calcium oxalate crystals can cause inflammation and tissue damage in the kidney, the use of herbal extracts with oxalatedegrading bacteria can be a new therapeutic approach to preventing the formation of kidney stones.

The effect of angiotensin 1-7 and losartan on renal ischemic/reperfusion injury in male rats.

Ischemia/reperfusion (I/R) is a major cause of acute kidney injury. Several studies have shown that renin angiotensin (Ang) system and activation of Ang II type 1 receptor (AT1) are involved in various forms of kidney diseases. Likewise, Ang 1-7 as a physiologic antagonist of AT1 and losartan could possibly protect the kidney against I/R damage. Therefore, we investigated renal injury by administering the drugs before and after I/R. Fifty-four male Wistar rats were randomly assigned to five groups as follows. 1, Sham operated; 2, saline group (as a control group); 3, losartan group; 4, Ang 1-7group; and 5, Ang 1-7 + losartan simultaneously. It should be noted that groups 2-5 consisted of two separate I/R-induced subgroups both receiving medication where the first groups received the treatment 15 min before induction of I/R while the medications were given to the second groups immediately after induction of I/R. Twenty four h after I/R, blood samples were collected, and then levels of serum urea nitrogen (BUN), creatinine (Cr), nitrite, malondialdehyde (MDA), lactate dehydrogenase (LDH) and total antioxidant capacity (TAC) were measured. Likewise, nitrite, MDA and TAC were measured in the homogenized kidney tissues. After the induction of I/R, the BUN, Cr, LDH, and kidney tissue damage score increased. Administration of Ang 1-7 alone or simultaneously with losartan decreased the levels of aforementioned factors. Also, kidney MDA and nitrate levels significantly increased after I/R induction (P < 0.05). According to the results of this study, it can be claimed that the effect of losartan in the presence of Mas receptor is statistically significant and kidney damage dramatically decreases.

Interaction of Sex Hormones and the Renin-Angiotensin System in Ovariectomized Rats Subjected to Ischemia-Reperfusion Induction.

BACKGROUNDS: Ischemia-reperfusion (IR) injuries occur in a variety of clinical conditions, which lead to kidney damage. Most of the tissue damages after IR are due to the activation of the renin-angiotensin system (RAS). Hence, in this study, the interaction of sex hormones and RAS in ovariectomized (OV) rats subjected to IR induction has been studied. MATERIALS AND METHODS: The animals were divided into different groups. Groups 1 (OV + E, OV rat + estradiol) and 2 (OV rat) each one consisted of three separate IR-induced subgroups treated with losartan, angiotensin 1-7 (Ang 1-7), and their combination, Group 3, as control and Group 4, as sham. Next, 72 h after IR, blood samples were collected, the right kidneys were homogenized, and left kidneys were fixed in 10% formalin. RESULTS: Findings show that serum blood urea nitrogen, creatinine, and kidney tissue damage score levels increased significantly with induction of IR (P < 0.05). Mean serum levels of these factors in OV + E groups are higher than those of the OV. The presence or absence of estradiol did not affect the levels of antioxidants in the different groups receiving Los, Ang 1-7, and their combination. Los, Ang 1-7, and their combination reduced serum and kidney malondialdehyde levels in both OV and OV + E groups. CONCLUSION: Estrogen not only fails to improve renal functioning but it can also exacerbate it. While the treatments used in this study, in the absence of estradiol, it had a better effect on kidney damages and improved its functions.

Simultaneous use of oxalate-degrading bacteria and herbal extract to reduce the urinary oxalate in a rat model: A new strategy

ABSTRACT Objective: Urinary stones with oxalate composition can cause kidney failure. Recent findings evidenced that probiotics are effective in reducing oxalate absorption in these subjects based on their high colonic absorption levels at baseline. The purpose of this study was to evaluate the effect of the simultaneous use of oxalate-degrading bacteria, Urtica dioica and T. terrestris extract in reducing urinary oxalate. Materials and Methods: Anti-urolithiatic activity of Urtica dioica and T. terrestris extract and probiotic by using ethylene glycol induced rat model. In this study, 4 strains of Lactobacillus and 2 strains of Bifidobacterium and also 2 strains of L. paracasei (that showed high power in oxalate degrading in culture media) were used. Male Wistar rats were divided into four groups (n=6). The rats of group-I received normal diet (positive control group) and groups-II (negative control group), III, IV rats received diet containing ethylene glycol (3%) for 30 days. Groups III rats received Urtica dioica and T. terrestris extract. Groups IV rats received extracts + probiotic for 30 days. Findings: The results show that the use of herbal extracts (Urtica dioica and T. terrestris) reduced the level of urinary oxalate and other parameters of urine and serum. Also, the accumulation of calcium oxalate crystals in the kidney tissue was significantly reduced. Conclusion: Considering that the formation of calcium oxalate crystals can cause inflammation and tissue damage in the kidney, the use of herbal extracts with oxalate degrading bacteria can be a new therapeutic approach to preventing the formation of kidney stones.

Effects of Eugenol on Pain Response to the Formalin Test and Plasma Antioxidant Activity in High Fructose Drinking Water in Male Rats.

BACKGROUND: Increased consumption of fructose in recent years has increased the risk of developing metabolic syndrome. In this syndrome, induction of oxidative stress, cellular dysfunction, and decrease of antioxidant capacity can change response to pain. Therefore, this study aims to investigate the antinociceptive and antioxidant effects of eugenol on metabolic syndrome induced by a fructose-rich diet in rats. METHODS: The rats were randomly assigned to five groups, to be under experiment for eight weeks. The first, control group, the second fructose 10% plus tween 0.5% (Fr + veh), the third fructose 10% (Fr), and the fourth fructose 10% plus a single dose of eugenol 100 mg/kg (Fr + EoS). However, the fifth obtained fructose 10% plus a continuous dose of eugenol 20 mg/kg/day (Fr + EoC) for the last 10 days of the experiment. After formalin test, blood samples were taken from the animals' hearts followed by analysis for biochemical factors. RESULTS: This study shows that fructose administration does not change any pain response and there are not any changes in pain response between Fr group and control group. However, treatment with single and continuous dose of eugenol in Fr + EoS and Fr + EoC groups significantly decreases response to pain in the first and second phase of formalin test in comparison with Fr group (P<0.05). Continuous does of eugenol improved serum malondialdehyde and total antioxidant capacity levels in Fr + Eoc group in comparison with Fr group. CONCLUSIONS: In the present work, new findings suggest the beneficial effects of eugenol in pain relief, improved serum glucose, insulin levels, and improved antioxidant activity in metabolic syndrome.

Sex Difference in Gentamicin-induced Nephrotoxicity: Influence of L-arginine in Rat Model.

BACKGROUND: L-arginine is an important precursor for the formation of nitric oxide (NO). According to previous studies, NO function is related to gender. Likewise, chronic renal diseases have lower prevalence in female. Gentamicin (GM) is an aminoglycoside antibiotic. According to some studies, males are more sensitive to GM renal nephrotoxicity. This study attempts to find protective effects of L-arginine on GM nephrotoxicity in male and female rats. METHODS: Male and female rats were divided into eight groups: Rats were randomly assigned to 8 groups each including both male and female rats. The first and second groups received vehicle (saline), the third and fourth groups received gentamicin (80 mg/kg), the fifth and sixth groups received L-arginine (150 mg/kg), and finally, seventh and eighth groups received gentamicin+ L- arginine. Next, 9 days after administering drugs, blood samples were collected from the heart. After making sacrifices, the level of blood urea, creatinine (Cr), nitrite, and malondialdehyde (MDA) was measured in serums. Likewise, nitrite and MDA were measured in the homogenized kidney tissue. RESULTS: GM significantly increased serum level of urea and Cr in male and female rats (P < 0.05). However, co-administration of GM + L-arginine significantly did not decrease urea and Cr level in male rats, whereas, in female rats, they significantly reduced (P < 0.05). In response to GM, renal MDA level increased in male and female rats (P < 0.05), and in the presence of GM + L-arginine, the level of MDA significantly decreased in both genders (P < 0.05). CONCLUSIONS: L-arginine demonstrated some protective effects in female rats but did not protect against GM nephrotoxicity in male rats for unknown reasons, probably related to the effects of sex hormones which needs further studies to be confirmed.

Cisplatin-Induced Nephrotoxicity; Protective Supplements and Gender Differences

Cisplatin (CDDP) has been widely used as a chemotherapeutic agent for solid tumors. The most common side effect of CDDP is nephrotoxicity, and many efforts have been made in the laboratory and the clinic to employ candidate adjuvants to CDDP to minimize this adverse influence. Many synthetic and herbal antioxidants as well as trace elements have been investigated for this purpose in recent years and a variety of positive and negative results have been yielded. However, no definitive supplement has so far been proposed to prevent CDDP-induced nephrotoxicity; however, this condition is gender related and the sex hormone estrogen may protect the kidney against CDDP damage. In this review, the results of research related to the effect of different synthetic and herbal antioxidants supplements are presented and discussed with suggestions included for future work.

High-Dose Estradiol-Replacement Therapy Enhances the Renal Vascular Response to Angiotensin II via an AT2-Receptor Dependent Mechanism.

Physiological levels of estrogen appear to enhance angiotensin type 2 receptor- (AT2R-) mediated vasodilatation. However, the effects of supraphysiological levels of estrogen, analogous to those achieved with high-dose estrogen replacement therapy in postmenopausal women, remain unknown. Therefore, we pretreated ovariectomized rats with a relatively high dose of estrogen (0.5 mg/kg/week) for two weeks. Subsequently, renal hemodynamic responses to intravenous angiotensin II (Ang II, 30-300 ng/kg/min) were tested under anesthesia, while renal perfusion pressure was held constant. The role of AT2R was examined by pretreating groups of rats with PD123319 or its vehicle. Renal blood flow (RBF) decreased in a dose-related manner in response to Ang II. Responses to Ang II were enhanced by pretreatment with estradiol. For example, at 300 ng kg(-1) min(-1), Ang II reduced RBF by 45.7 ± 1.9% in estradiol-treated rats but only by 27.3 ± 5.1% in vehicle-treated rats. Pretreatment with PD123319 blunted the response of RBF to Ang II in estradiol-treated rats, so that reductions in RBF were similar to those in rats not treated with estradiol. We conclude that supraphysiological levels of estrogen promote AT2R-mediated renal vasoconstriction. This mechanism could potentially contribute to the increased risk of cardiovascular disease associated with hormone replacement therapy using high-dose estrogen.

Role of Mas receptor in renal blood flow response to angiotensin (1-7) in male and female rats.

Epidemiologic and clinical studies have shown that progression of renal disease in male is faster than that in female. However, the exact mechanisms are not well recognized. Angiotensin (1-7) (Ang 1-7) receptor, called "Mas", is an element in the depressor arm of renin angiotensin system (RAS), and its expression is enhanced in females. We test the hypothesis that Mas receptor (MasR) blockade (A779) attenuates renal blood flow (RBF) in response to infusion of graded doses of Ang 1-7 in female rats. Male and female Wistar rats were anesthetized and catheterized. Then, the mean arterial pressure (MAP), RBF, and controlled renal perfusion pressure (RPP) responses to infusion of graded doses of Ang 1-7 (100-1000 ng/kg/min i.v.) with and without A779 were measured in the animals. Basal MAP, RPP, RBF, and renal vascular resistance (RVR) were not significantly different between the two groups. After Ang 1-7 administration, RPP was controlled at a constant level. However, RBF increased in a dose-related manner in response to Ang 1-7 infusion in both male and female rats (Pdose<0.0001), but masR blockade significantly attenuated this response only in female (Pgroup=0.04) and not male (Pgroup=0.23). In addition, A779 increased the RBF response to Ang 1-7 to a greater extent. This is while the increase in male was not significant when compared with that in female (Pgender=0.08). RVR response to Ang 1-7 was insignificantly attenuated by A779 in both genders. The masR differently regulated RBF response to Ang 1-7 in the two genders, and the effect was greater in female rats. The masR may be a target for improvement of kidney circulation in renal diseases.

Role of Angiotensin Type 2 Receptor on Nitric Oxide Production Response to Angiotensin II Administration in Ovariectomised Rats Treated with Estradiol.

BACKGROUND: Renin-angiotensin system activity is gender related. The vasodilatory response of angiotensin II (AngII) angiotensin type 2 receptor (AT2R) may involve nitric oxide (NO) production. We attempted to find the role of AT2R on NO formation response to AngII administration in ovariectomised rats treated with estradiol (OVE). METHODS: A total of 33 female Wistar rats were divided into 3 groups; intact animals, ovariectomised treated with placebo (OVX) and OVE. At 2 weeks later, all animals were subjected to anesthetize and catheterize and each group was divided into two subgroups that received AT2R antagonist (PD123319) or vehicle. Each animal was subjected to 1 h continuous infusion of AngII (~20 µg/kg/h) and the level of NO metabolite (nitrite) was measured before and after AngII infusion. RESULTS: At the presence of AT2R, the serum level of nitrite in response to AngII administration in OVE groups increased significantly (P < 0.05). CONCLUSIONS: However, this increase was abolished by AT2R antagonist. It seems that AT2R involves nitrite production response to AngII in OVE.

N-acetylcysteine Prevents Kidney and Lung Disturbances in Renal Ischemia/Reperfusion Injury in Rat.

BACKGROUND: One of the most common causes of acute kidney injury (AKI) is kidney ischemia/reperfusion injury (IRI). The distant organ injury such as acute lung injury is one of the side effects of AKI or kidney IRI. In this study, we performed bilateral renal IRI in rats and the protective role of N-acetylcysteine (NAC) in kidney and lung was investigated. METHODS: Rats (n = 30) were randomly assigned to four experiment groups. The group 1 was assigned as sham-operated group. Before kidney IRI performance, the others groups were treated with saline (group 2), 150 mg/kg (group 3) or 500 mg/kg (group 4) of NAC, and the treatment were continued daily after IRI for next 3 days. At day 3, the all groups' animals were subjected for the measurements. RESULTS: The serum level of blood urea nitrogen (BUN) and creatinine (Cr) in the control group increased significantly (P < 0.05), and administration of NAC (150 mg/kg) decreased the serum levels of Cr and BUN. However, only the serum level of Cr decreased significantly (P < 0.05). NAC did not improve kidney weight and damage; however, its low dose (150 mg/kg) attenuated the lung injury score (P < 0.05) when compared with the control group. No significant differences were observed in lung water content and endothelial permeability, serum levels of malondialdehyde and nitrite between the groups. CONCLUSIONS: Low dose of NAC as a protectant agent may protect the kidney function and lung tissue damage after kidney IRI.

Sex differences in protective effect of recombinant human erythropoietin against cisplatin-induced nephrotoxicity in rats.

INTRODUCTION: The protective role of recombinant human erythropoietin (RHE) against cisplatin-induced nephrotoxicity has been reported, but the role of sex differences is not clearly known. The aim of this study was to determine the sex-based difference in the protective effect of RHE against cisplatin-induced nephrotoxicity. MATERIALS AND METHODS: Thirty-three Wistar rats were divided into 6 groups. According to protocol l, male and female rats were treated with RHE (100 IU/kg/d) for 3 days and then received a single dose of cisplatin (7 mg/kg). According to protocol 2, the rats received the same single dose of cisplatin and then were treated with RHE for 7 days. Two other groups of male and female rats received a similar regimen of protocol 2 except for saline instead of RHE. All the animals were sacrificed 1 week after cisplatin administration. RESULTS: All of the experimental animals experienced weight loss. The percentage change of weight in male rats with protocol 1 was significantly less than that in male rats in protocol 2 and control groups. However, in female groups, the percentage of change in weights was slightly higher with protocol 2 than with protocol 1 and control treatment. Administration of RHE significantly decreased changes in serum creatinine, BUN, and malondialdehyde levels in male rats, but not in females. No significant difference was observed in serum nitrite level, kidney weight, and kidney damage score between the groups. CONCLUSIONS: This study suggested that erythropoietin may lead to different responses against cisplatin-induced nephrotoxicity in male and female rats.

Evidence against protective role of sex hormone estrogen in Cisplatin-induced nephrotoxicity in ovarectomized rat model.

BACKGROUND: Cisplatin (CP) is an effective drug in cancer therapy to treat the solid tumors, but it is accompanied with nephrotoxicity. The protective effect of estrogen in cardiovascular diseases is well-documented; but its nephron-protective effect against CP-induced nephrotoxicity is not completely understood. MATERIALS AND METHODS: Thirty ovarectomized Wistar rats were divided in to five groups. Groups 1-3 received different doses of estradiol valerate (0.5, 2.5 and 10 mg/kg/week) in sesame oil for 4 weeks, and at the end of week 3, a single dose of CP (7 mg/kg, intraperitoneal [IP]) was administrated. Group 4 (positive control) received the same regimen as group 1-3 without estradiol without vehicle. The negative control group (Group 5) received sesame oil during the study. The animals were sacrificed 1 week after CP injection for histopathological studies. RESULTS: The serum level of blood urea nitrogen and creatinine, kidney tissue damage score (KTDS), kidney weight and percentage of body weight change in CP-treated groups significantly increased (P < 0.05), however, there were no significant differences detected between the estrogen-treated groups (Groups 1-3) and the positive control group (Group 4). Although, estradiol administration enhanced the serum level of nitrite, it was not affected by CP. Finally, significant correlation between KTDS and kidney weight was detected (r (2) = 0.63, P < 0.01). CONCLUSION: Estrogen is not nephron-protective against CP-induced nephrotoxicity. Moreover, it seems that the mechanism may be related to estrogen-induced oxidative stress in the kidney, which may promote the nephrotoxicity.

The effects of unripe grape extract on systemic blood pressure, nitric oxide production, and response to angiotensin II administration.

BACKGROUND: Hypertension is the most common disease in the world. In Iranian folk medicine, unripe grape juice has been used as antihypertention remedy, but no data is documented for this popular belief. This study was designed to determine the effect of unripe grape extract (UGE) on blood pressure and the response to angiotensin II in rat. MATERIALS AND METHODS: Unripe grape was collected, air dried, and extracted and concentrated. Four groups of Wistar rats received single doses of 125, 250, and 500 mg/kg of UGE or saline, respectively. The direct blood pressure and the serum nitrite level were measured one hour post UGE administration. The animals also were subjected to the infusion of various angiotensin II concentrations (100, 300, and 1000 µg/kg/min), and blood pressure was determined. RESULTS: Mean arterial, systolic, and diastolic pressures (MAP, SP, and DP) in all UGE treated groups were less than the control group, but only at the dose of 125 mg/kg (Group 1) they were significantly different (P < 0.05). The level of nitrite in groups 1-3 were significantly greater than the control group (P < 0.05). No significant differences were detected for the MAP, SP, and DP to different concentrations of angiotensin II among these groups. CONCLUSION: UGE potentially attenuate MAP, SP, and DP via vasodilatation induced by nitric oxide production.