Absolute Kidney Weights Research Articles

The consequences of environment-induced heat stress on the kidney in female mice

Environment-induced heat stress (EIHS) is caused by a sustained elevation in body temperature, due to prolonged exposure to excess heat and humidity. Given the present and increasing frequency of EIHS and the gap in knowledge regarding EIHS-mediated impacts to the kidney, the purpose of this investigation was to determine the extent to which EIHS alters kidney health. We hypothesized EIHS would cause kidney injury and cellular dysfunction. To test this hypothesis, 7 wk old C57 female mice were assigned to either EIHS (n=14; 36.7 ± 0.16 °C, 36.3 ± 0.5 % humidity) or thermoneutral (TN) conditions (n=12, 31.2 ± 1.01 °C, 35 ± 0.7% humidity) for 24 h, kidneys were removed, weighed, and were either fixed for histology or frozen for biochemical measures. Environment-induced HS increased rectal temperature by 2.1 °C (p< 0.001), decreased body weight by 10% (p=0.03), and decreased absolute kidney weight (10%; p=0.02) compared to TN. Environment-induced HS increased relative protein abundance of heat shock proteins 70 (48%, p<0.01), 90 (37%, p<0.01), and 60 (36%, p=0.02), as well as heat shock factor 1 (2-fold, p=0.02) compared to TN. Histological inspection revealed EIHS animals had increased vacuolation in the proximal convoluted tubules (p<0.01) compared to TN animals. Using a western blot approach, we measured biomarkers of kidney tubular health and discovered EIHS increased protein abundance of NGAL (88%, p<0.01), IL-10 (36%, p=0.05), IL-6 (46%, p<0.01), MCP-1 (74%, p=0.04), and L-FABP (99%, p<0.01), which are suggestive of kidney injury. Environment-induced HS increased markers of inflammatory signaling including TLR4 (44%, p=0.04), phosphorylated (p-) NFκB (93%, p<0.01), p-JNK (54 kD; 51%, p=0.02), p-JNK (46 kD, 35%, p=0.02), AP-1 (33%, p=0.02), and TNFα (39%, p=0.05). Endoplasmic reticulum stress was increased by EIHS as Bip, p-IRE1α, Perk, XBP1s, ATF4, and CHOP were increased 27-190% (p<0.05-0.01) compared to TN animals. Markers of mitochondrial abundance remained similar between groups; however, EIHS may alter mitochondrial fusion and fission as Opa1 (71%, p=0.01), MFN2 (29%, p=0.04) and DRP1 (59%, p=0.04) were increased compared to TN; however, MFN1, FIS1, and p-DRP1 were similar between groups. Collectively, these data suggest that 24 h of EIHS causes kidney injury, but may also be suffcient to initiate changes that contribute to acclimation. This study was supported by USDA 2020-02716. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Pharmacokinetics and 28-day repeated-dose toxicity of enniatin B after oral administration in mice.

Enniatins are emerging mycotoxins that contaminate foods. The present study investigated the oral pharmacokinetics and 28-day repeated-dose oral toxicity of enniatin B (ENNB) in CD1 (ICR) mice. In the pharmacokinetic study, male mice received a single oral or intravenous dose of ENNB [30mg/kg body weight (BW) and 1mg/kg BW, respectively]. After oral dosing, ENNB exhibited 139.9% bioavailability, a 5.1-h elimination half-life, 5.26% fecal excretion from 4 to 24h post-dose, and upregulation of Cyp7a1, Cyp2a12, Cyp2b10, and Cyp26a1 in the liver 2h post-dosing. In the 28-day toxicity study, ENNB was administered to male and female mice by oral gavage at 0, 7.5, 15, and 30mg/kg BW/day. Females (7.5 and 30mg/kg) showed dose-unrelated decreased food consumption without accompanying changes in clinical parameters. Males (30mg/kg) showed low red blood cell counts and high blood urea nitrogen levels and absolute kidney weights; however, other related parameters including the histopathology of systemic organs/tissues were unchanged. These results suggest that ENNB may not induce toxicity after 28 days of oral administration in mice, despite high absorption. The no-observed-adverse-effect level of ENNB after 28 days of repeated oral doses was 30mg/kg BW/day for both sexes of mice.

Nephroprotective Effects of L-Arginine against Chemotherapy Induced Acute Kidney Injury in Wistar Rats

Objective To evaluate the protective role of L-Arginine in cisplatin induced acute renal injury through assessment of renal, oxidative stress and inflammatory markers in albino wistar rats.
 Methods: Quasi-experimental study was conducted at the department of physiology and postgraduate research laboratory at Isra University, Hyderabad, Sindh from April 2019 to September 2019. Thirty male Albino wistar rats were selected through non-random purposive sampling and divided equally into three different groups: Group-A (Control group), Group-B (experimental group) received Cisplatin alone and Group-C (experimental group) received Cisplatin along with arginine. After sacrificing the animals, blood samples were collected through cardiac puncture while renal histopathological analysis was under the light microscope. The changes in severity were observed using a graded scale. Data was analysed using SPSS v23.0.
 Results: There was a statistically significant (p-value <0.05) decline in the bodyweight and rise in absolute kidney weight of group B in comparison with other two group. Moreover, significant rise (p-value <0.05) in serum renal markers was observed in group B while significant decline (p-value <0.05) in these serum renal markers in group C compared with group B. Furthermore, prominent demage in normal renal histology in group B rats while restoration of renal histology was demonstrated in group C rats.
 Conclusion: The present study concludes that L-Arginine exerts an anti-oxidative, anti-inflammatory and nephro-protective effect for renal tissue damage caused by Cisplatin.
 Keywords: Acute Kidney Injury, Antioxidant, Cisplatin, L-Arginine, Oxidative stress

Protective effects of vitamin E on aluminium chloride-induced liver and kidney damage in rats

Aluminium is present in many manufactured foods and medicines and is also used in water purification. It is known that aluminium causes oxidative stress. Therefore, the present study was undertaken to determine the effectiveness of vitamin E (VE) in modulating the toxicity of aluminium chloride (AlCl3) on biochemical parameters, antioxidant enzymes and lipid peroxidation in serum and different organs (liver and kidney) of male Wistar rats. 24 rats (150-180g) were divided into four groups of six animals each : control ; Al was administered intraperitoneally (50 mg/kg/bw, one times a week) ; VE was given orally at a daily dose (100 mg/kg/bw) and Al+VE group. The experiment during for 90 days. AlCl3 caused a decreased in body weight consumption along with increased in the absolute and relative liver and kidney weights. TBARS level was increased, and the enzymes activities of CAT and SOD were decreased in liver and kidney of rats treated with AlCl3. While, TBARS was decreased and the antioxidant enzymes were increased in rats treated with VE. The hepatic and renal damage induced by Al was evidenced by a increase in the levels of serum AST, ALT, LDH, ALP, γGT, glucose, urea, creatinine and bilirubin, while total protein and albumin were decreased due to AlCl3 administration. These parameters indicated the extent of oxidative damage in liver and kidney, thus confirming the histology results in these organs. It can be concluded in this study that presence of VE effectively atte-nuated AlCl3 induced hepatotoxicity and nephrotoxicity in rats. It has benefi-cial influences and protective effect against AlCl3 toxicity.

Evaluation of 2-methoxy-4-nitroaniline (MNA) in hypersensitivity, 14-day subacute, reproductive, and genotoxicity studies

2-Methoxy-4-nitroaniline (MNA), an intermediate in the synthesis of azo dyes used in textiles and paints, is structurally similar to carcinogenic anilines. Human exposure occurs primarily in the occupational setting through handling of dye dust, and through use and disposal of MNA-containing products. MNA has been reported to induce contact hypersensitivity in a human, myocardial necrosis in rats, and bacterial mutagenicity. This study assessed the subacute toxicity, genotoxicity, contact hypersensitivity, and reproductive toxicity of MNA in rodents in an effort to more fully characterize its toxicological profile. B6C3F1/N mice were exposed to 0, 650, 1250, 2500, 5000, or 10,000 ppm MNA by dosed feed for 14-days to evaluate subacute toxicity and histopathological endpoints. In female mice, decreased body weight (13.5 %) and absolute kidney weight (14.8 %), compared to control, were observed at 10,000 ppm MNA; increased relative liver weight (10–12 %), compared to control, occurred at 5,000–10,000 ppm MNA. In male mice, absolute (15 %) and relative liver weights (9–13 %) were increased at 2,500−5,000 ppm and 1250–10,000 ppm MNA, compared to control, respectively. In both sexes of mice, minimal elevations of hemosiderin pigmentation (a breakdown product of erythrocytes), relative to control, were observed in the liver (10,000 ppm); minimal to moderate elevations of hemosiderin pigmentation (5,000–10,000 ppm) and minimal increases in hematopoietic cell proliferation occurred in the spleen (≥ 1250 ppm). In a reproductive toxicity study, timed-mated female Harlan Sprague Dawley rats were exposed to 0–10,000 ppm MNA by dosed feed from gestation day 6 through postnatal day (PND) 21. Decreases in mean litter weights were observed at 5000 ppm MNA, compared to control, beginning at PND1. To evaluate potential contact hypersensitivity, MNA (2.5–50 %, in dimethylformamide) was applied to the dorsa of both ears of female Balb/c mice once daily for three days. The increase observed in lymph node cell proliferation (10–50 % increase in thymidine uptake compared to control) did not reproducibly achieve the Sensitization Index (SI) 3 level, and there was no ear swelling evident following sensitization with 10–50 % MNA and challenge with 25 % MNA in the mouse ear swelling test. In bacterial mutagenicity assays, MNA (250−1000 μg/plate) induced significant increases, compared to control, in mutant colonies with and without metabolic activation enzymes in Salmonella typhimurium strains TA100 and TA98. These data indicate that MNA is genotoxic, and may induce erythrocyte damage and reactive phagocytosis by macrophages in the liver and spleen.

Age and Gender-Related Changes in Renal Haemodynamics of Albino Rats: The Possible Role of Cytokines and Prostaglandins

AbstractBackground: The normal aging process leads to changes in kidney morphology, hemodynamics and function, which are influenced by several factors, including gender. Females develop less age-dependent loss of renal function due to cardiorenal protective effects of estrogens.Aim of Study: The aim of this study was to elucidate the age and gender-related changes in some renal haemodynamics in albino rats with special focusing on the role of cytokines and prostaglandins in establishment of such changes.Material and Methods: Sixty albino rats (30 males & 30 females) of local strain were divided into 2 major groups (Group I of male rats and Group II of female rats) was further subdivided into 3 subgroups: Young (4wk), young adult (3mo) and old (25mo). Body Weight (BW) and absolute Kidney Weight (KW) were measured. The Systolic Blood Pressure (SBP) of the rats was measured by the rat-tail plethysmography technique using a tail-cuff sphygmomanometer. The Renal Blood Flow Velocity (RBFV) and Renal Vascular Resistance (RVR) were measured using bi-directional blood flow meter with FFT-analysis. The blood samples were collected after a period of overnight fasting, left to be clotted, centrifuged and serum was separated for measurement of serum testosterone in male rats, serum estrogen in female rats, creatinine clearance, serum IL1beta, IL6 and serum PGE.Results: The aging of male rat group is accompanied by change in the renal hemodynamic and some blood measure-ments. This is represented by significant increase in systolic blood pressure, renal vascular resistance, serum PGE, serum interleukin1-b & 6, impaired renal function and significant decrease of renal blood flow. It was observed that the old female group had decreased in estrogen hormone level, which led to increase in systolic blood pressure, renal vascular resistance, serum PGE, serum interleukin1-b & 6 and signif-icant decrease renal blood flow.Conclusion: Aging has a significant influence in renal hemodynamic (decrease of renal blood flow and increase of renal vascular resistance) and also, serum interleukin1-b & 6 have a role in this change accompanied with pathophysiology of aging. Female is more protected from complications of the kidney aging than male due to the previous effect of estrogen hormone.

Royal jelly attenuates cadmium-induced nephrotoxicity in male mice

Cadmium exposure induces nephrotoxicity by mediating oxidative stress, inflammation, and apoptosis. The purpose of this study was to examine the protective effect of royal jelly on Cd-induced nephrotoxicity. Adult male mice were distributed randomly into 4 clusters: untreated, royal jelly-treated (85 mg/kg, oral), CdCl2-treated (6.5 mg/kg, intraperitoneal), and pretreated with royal jelly (85 mg/kg) 2 h before CdCl2 injection (6.5 mg/kg, intraperitoneal) for seven consecutive days. Cd concentration in the renal tissue and absolute kidney weight of the Cd-treated mice were significantly higher than those of control group. The levels of kidney function markers, kidney injury molecules-1 (KIM-1), metallothionein, lipid peroxidation, nitric oxide, tumor necrosis factor-α, interleukin-1β, and the apoptosis regulators Bax and caspases-3 also increased significantly in the renal tissue of Cd-treated mice, whereas the levels of glutathione, antioxidant enzyme activities, and the apoptosis inhibitor Bcl-2 were significantly reduced in the renal tissue of Cd-treated group. Histopathological studies showed vacuolation and congested glomeruli in the kidney tissue of Cd-treated mice. However, all aforementioned Cd-induced changes were attenuated by pretreatment with royal jelly. We therefore concluded that royal jelly attenuated Cd-induced nephrotoxicity and it is suggested that this nephroprotective effect could be linked to its ability to promote the nuclear factor erythroid 2–related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway.

EFFECT OF SILYMARIN EXTRACTED FROM SILYBUM MARIANUM ON NICKEL HEMATOTOXICITY AND NEPHROTOXICITY IN MALE ALBINO WISTAR RATS

Objective: The objective of this study was to investigate the effect of silymarin extract from Silybum marianum against nickel-induced alterations in haematological indices, kidney dysfunction and renal antioxidant defence system.Methods: Male albino Wistar rats were divided into four groups seven each. Control, silymarin, nickel and nickel plus silymarin. Silymarin was administrated orally (100 mg/kg b. wt) and nickel as nickel sulfate (NiSO4 6H20) was given intraperitoneally (20 mg/kg b. wt) at alternative days. The experiment continued for three consecutive weeks. Body weight was recorded regularly. After overnight fasting, animals were killed and serum creatinine, serum urea, serum uric acid, hematological parameters and renal antioxidant markers were determined.Results: The treatment with nickel led to a significant decrease in body weight with an increase in both absolute and relative kidney weights and a significant increase in renal markers, which confirmed by histopathological alteration. A microcytic anemia was also observed, which was manifested by a reduction of red blood cells count (RBC), hemoglobin (Hb) concentration, platelet counts (Plt), hematocrit and white blood cells counts (WBC). The level of lipid peroxidation was increased. Whereas, GSH concentration and enzymatic antioxidants SOD, GSH-Px and CAT activities were decreased. The co-treatment with methanolic extract of milk thistle attenuated the variation in the hematological and renal markers, decreasing renal lipid peroxidation (p<0.05) with a concomitant increasing reduced glutathione content (p<0.01) and restoring the antioxidant enzymes (SOD, CAT, GSH-Px) in kidney, as well as an improvement in histological changes compared to those previously noticed in nickel group.Conclusion: To conclude, these findings demonstrated that silymarin extract effectively improved heamatotoxicity and nephrotoxicity caused by nickel.

EFFECTS OF ERUCA SATIVA SEED OIL ON THE HISTOLOGY OF LIVER AND KIDNEY RATS

The objective of this study was to investigate the possible ameliorative effect of Eruca sativa seed oil on the histopathological structure of the liver and kidneys of male albino rats. A total of fourteen rats were grouped into two groups of 7 rats each. Group 1 rats served as control, while group 2 received 2 ml/kg B.W. of Eruca sativa seed oil, daily for four weeks through the oral route (i.g.). A significant decrease (P < 0.05) in the absolute liver weights was observed in the treated group as compared with the control (9.66 ± 0.55 and 10.00 ± 2.07, respectively). Also, the absolute kidney weights were found significantly decreased (P < 0.05) after treatment as compared to controls (1.70 ± 0.09 and 2.16 ± 0.46, respectively). In the control group, the relative liver index (%) was 3.86 grams and the relative kidney index (%) was 0.83 grams. In the experimental group, the relative indexes were 4.05 grams and 0. 71 grams, for liver and kidney, respectively. Light microscopic examination of indicated some histopathological changes in both studied organs. In liver, congestion in the blood vessels and sinusoid were observed. Moreover, the obvious change in the kidneys was congestion. In conclusion, this study shows that daily administration of Eruca sativa seed oil at a dose 2 ml/kg B.W., for 4 weeks, could pathologically affect some vital internal organs, such as liver and kidneys causing alterations in their histological structure. So, it is recommended to be used at low suitable dose.

Plasma and kidney distribution of emamectin benzoate in rats by ultra-performance liquid chromatography–tandem mass spectrometry, and protective effect of vitamin C

Aim Emamectin benzoate (Proclaim ® ) is a macrocyclic lactone semi-synthetic derivative of the avermectins. It is a mixture of at least 90% avermectin B1a benzoate (MAB1a) and at most 10% MAB1b salts [1] . The aim of this study is to investigate the plasma and kidney distribution of EMB in rats by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) and to evaluate the protective effects of vitamin C against toxicity of this biopesticide after a subacute toxicity study. Methods Male rats ( n = 21) were allocated into 3 groups of seven each: group I served as control rats; group II was given daily EMB at dose of 10 mg/kg b.w. by gavage; group III received EMB (10 mg/kg b.w.) and were co-administered with vitamin C intraperitoneally (200 mg/kg/day) during 28 days. Rats were followed-up for an additional 14 day-period to detect delayed occurrence or persistence of toxic effects. The residual concentrations of emamectin benzoate mixture B1a and B1b were determined in control, EMB, and EMB + VitC groups. Plasma and tissue homogenates were pretreated by protein precipitation with acetonitrile. In plasma samples at 14, 21, 28 and 42 days of experiment and in kidneys at 28 and 42 days of experiment, B1a and B1b concentrations were determined. Results A decrease in body weight, absolute and relative kidney weights in EMB-treated rats and a significant increase in EMB +VitC group, after 28 and 42 days of experiment, were observed. Emamectin B1a and B1b were found in all plasma samples of EMB and EMB + VitC rats in a time-dependent manner at 14 days [EMB group (B1a: 531.95 ± 98.31; B1b: 20.25 ± 10.71) and EMB + VitC (B1a: 436.70 ± 200.39; B1b: 15.12 ± 2.97)], 21 days [EMB group (B1a: 566.29 ± 103.91; B1b: 19.73 ± 3.00) and EMB + VitC group (B1a: 315.97 ± 73.72; B1b: 16.02 ± 4.00)] and 28 days of treatment [EMB group (B1a: 626.35 ± 159.32; B1b: 23.03 ± 8.19) and EMB + VitC group (B1a: 368.50 ± 152.22; B1b: 14.88 ± 7.28)]. However, those concentrations were higher in the EMB-treated group when compared with the EMB + VitC group. Moreover, at 42 days, there was no more residue detectable in the plasma of all treated rats. In EMB-treated rats, the drug kidney concentrations were significantly lower in EMB + VitC compared with EMB-treated rats at 28 days [EMB group (B1a: 24.98 ± 1.85; B1b: 3.63 ± 0.34) and EMB + VitC (B1a: 14.14 ± 1.24; B1b: 1.26 ± 0.29)] and 42 days post-treatment [EMB group (B1a: 0.87 ± 0.30; B1b: 0.04 ± 0.01) and EMB + VitC (B1a: 0.31 ± 0.15; B1b: 0.01 ± 0.00)]. Elevated concentrations of residues in plasma and kidneys of EMB-treated rats compared to those in EMB + Vit C-treated rats suggest an ameliorative effect of vitamin C. Conclusion EMB was widely distributed in rat plasma and kidneys and its concentrations in kidney increased in a time-dependent manner. Vitamin C, when administered at moderate doses and maintained for a long period, could reduce the accumulation of EMB in plasma and kidneys.

The sub-chronic oral toxicity of dearomatized hydrocarbon solvents in Sprague–Dawley rats

Dearomatized hydrocarbon solvents in the C9–C14 aliphatic carbon number range were developed as alternatives to traditional solvents such as mineral spirits, but with lower aromatic content. Previous subchronic toxicity studies (both published and unpublished) have shown minimal to no systemic effects with exposure to dearomatized solvents, with the exception of rat-specific renal effects that have no relevance to humans. In this study, Sprague–Dawley rats were exposed to 0, 500, 2500 and 5000mg/kg/day of a C10–C13 dearomatized solvent for 90days by oral gavage. Liver enlargement and centrilobular hypertrophy were observed in all treated groups but were considered adaptive consequences of hydrocarbon-induced microsomal enzyme induction. Clinical chemistry data showed elevations of alanine aminotransferase (ALT), gamma glutamyltransferase (GGT) and total bilirubin in mid (ALT alone) and high dose groups, suggesting potential hepatobiliary effects with high dose exposure. Increased absolute kidney weight changes were restricted to male rats and associated with renal lesions indicative of alpha-2u globulin-mediated nephropathy. One limitation of the NOAEL/LOAEL approach in selecting points of departure for exposure limits is its dependence on dose selection/study design. Hence, a more robust approach that incorporates all data points on the dose–response curve, such as bench mark modeling, is preferred. Overall, benchmark dose analysis estimated a BMDL of 1857mg/kg/day based on increased serum ALT. This value is consistent with studies of similar hydrocarbon substances showing a lack of systemic effects at doses up to 1000mg/kg/day in the same rat strain.

The relationship between chemical-induced kidney weight increases and kidney histopathology in rats.

The kidney is a major site of chemical excretion, which results in its propensity to exhibit chemically-induced toxicological effects at a higher rate than most other organs. Although the kidneys are often weighed in animal toxicity studies, the manner in which these kidney weight measurements are interpreted and the value of this information in predicting renal damage remains controversial. In this study we sought to determine whether a relationship exists between chemically-induced kidney weight changes and renal histopathological alterations. We also examined the relative utility of absolute and relative (kidney-to-body weight ratio) kidney weight in the prediction of renal toxicity. For this, data extracted from oral chemical exposure studies in rats performed by the National Toxicology Program were qualitatively and quantitatively evaluated. Our analysis showed a statistically significant correlation between absolute, but not relative, kidney weight and renal histopathology in chemically-treated rats. This positive correlation between absolute kidney weight and histopathology was observed even with compounds that statistically decreased terminal body weight. Also, changes in absolute kidney weight, which occurred at subchronic exposures, were able to predict the presence or absence of kidney histopathology at both subchronic and chronic exposures. Furthermore, most increases in absolute kidney weight reaching statistical significance (irrespective of the magnitude of change) were found to be relevant for the prediction of histopathological changes. Hence, our findings demonstrate that the evaluation of absolute kidney weight is a useful method for identifying potential renal toxicants.

Age-Specific Absolute and Relative Organ Weight Distributions For B6C3F1 Mice

The B6C3F1 mouse is the standard mouse strain used in toxicology studies conducted by the National Cancer Institute (NCI) and the National Toxicology Program (NTP). While numerous reports have been published on growth, survival, and tumor incidence, no overall compilation of organ weight data is available. Importantly, organ weight change is an endpoint used by regulatory agencies to develop toxicity reference values (TRVs) for use in human health risk assessments. Furthermore, physiologically based pharmacokinetic (PBPK) models, which utilize relative organ weights, are increasingly being used to develop TRVs. Therefore, all available absolute and relative organ weight data for untreated control B6C3F1 mice were collected from NCI/NTP studies in order to develop age-specific distributions. Results show that organ weights were collected more frequently in NCI/NTP studies at 2-wk (60 studies), 3-mo (147 studies), and 15-mo (40 studies) intervals than at other intervals, and more frequently from feeding and inhalation than drinking water studies. Liver, right kidney, lung, heart, thymus, and brain weights were most frequently collected. From the collected data, the mean and standard deviation for absolute and relative organ weights were calculated. Results show age-related increases in absolute liver, right kidney, lung, and heart weights and relatively stable brain and right testis weights. The results suggest a general variability trend in absolute organ weights of brain < right testis < right kidney < heart < liver < lung < spleen < thymus. This report describes the results of this effort.

Protective effects of selenium on methimazole nephrotoxicity in adult rats and their offspring

This study aims to investigate the improving effects of selenium on methimazole-induced kidney impairments in adult rats and their pups. The animals were randomly divided into four groups of six each: group I served as control which received standard diet; group II received only methimazole in drinking water as 250 mg/l; group III received both methimazole (250 mg/l, orally) and selenium (0.5 mg/kg of diet); group IV served as a positive control and received selenium (0.5 mg/kg of diet) as sodium selenite (Na 2SeO 3). Treatments were started from the 14th day of pregnancy until day 14 after delivery. In the methimazole-treated group, body and absolute kidney weights decreased in pups and their mothers when compared to control. Daily urine volume, plasma creatinine levels were higher, while urinary levels were lower than in control. Besides, antioxidant enzyme activities, superoxide dismutase, catalase and glutathione peroxidase decreased. Lipid peroxidation recorded an increase revealed by high kidney malondialdehyde levels, while those of plasma and urinary uric acid showed a significant decline. Methimazole-treated rat kidneys exhibited leucocytic infiltrations, vascular congestion and narrowed Bowman's space. Co-administration of selenium through diet improved all the parameters cited above in adult rats and their progeny. Nevertheless, the distorted histoarchitecture in rat kidney was alleviated by selenium treatment. It can then be concluded that selenium is an important protective element that may be used as a dietary supplement against kidney impairments.

Hypoglycemic and antihyperglycemic effect of Begonia malabarica Lam. in normal and streptozotocin induced diabetic rats

Aim of the studyThe stem of Begonia malabarica was used traditionally by the Malasar tribe to treat diabetes. To validate the hypoglycemic and antihyperglycemic effects of the hexane, ethylacetate and methanol extracts obtained from an ethnomedicinal plant, Begonia malabarica. Materials and methodsThe doses for the study were fixed based on Irwin test. The hypoglycemic effect of hexane, ethylacetate and methanol extracts of Begonia malabarica stems were studied in normal animals. The antihyperglycemic effect of the methanol extract was studied in streptozotocin induced diabetic rats. ResultsIn normal rats the treatment with the methanol extract of Begonia malabarica had shown a highly significant reduction (16.54 and 34.47%) in plasma glucose levels from the 0h values at the dose of 100 and 200mg/kg respectively. In streptozotocin induced diabetic rats the body weight of the Begonia malabarica methanol extract treated animals had shown a significant increase (13.38% at 200mg/kg) after 4 weeks treatment. The plasma glucose levels were reduced significantly by 46.57 and 50.20% after 4 weeks treatment at 100 and 200mg/kg respectively. Likewise the absolute kidney weight was also reduced in a significant manner. After 25 days treatment the Begonia malabarica methanol extract treated animals had shown low fasting plasma glucose levels (54.29, 61.34% in 100 and 200mg/kg) and reduced postprandial plasma glucose levels (54.23, 65.96% in 100 and 200mg/kg) when compared with diabetic control values. Serum insulin levels and liver glycogen levels were increased to 40.04 and 42.18% in 200mg/kg Begonia malabarica methanol extract treated animals respectively. The treatment with Begonia malabarica methanol extract did not change the triglycerides and total cholesterol levels. The urea and creatinine levels were also reduced significantly by this treatment. The reduction in SGPT levels indicated the absence of toxicity of Begonia malabarica extract at this dose level. ConclusionThis study supports the use of Begonia malabarica by the Malasar tribe for the treatment of diabetes. Fractionation of this extract may yield novel prototypes to manage diabetes mellitus.

Reply to: Schreuder

reply: In aging male Wistar rats, renal injury develops spontaneously ([2][1]). It is gratifying that Dr. Schreuder is intrigued by our recent finding of a protective effect of early postnatal protein restriction (i.e., during lactation) on the spontaneous development of renal injury in male Wistar

Evaluation of the Effects of Subchronic Oral Administration of n-Butyl Maleate in Sprague-Dawley Rats

n-Butyl maleate, also referred to as monobutyl maleate, is an ester of maleic acid, which is used as a counterion in the pharmaceutical industry. While substantial published data exist on short-term treatment, maleic acid-induced renal toxicity in the rat, no toxicity data are available on the monobutyl ester. This study evaluated the oral subchronic nephrotoxicity potential of n-butyl maleate administered to Sprague-Dawley rats (10/males and females/group) at doses of 0 (vehicle control), 10, 30, or 60 mg/kg/d for 2 wk. Statistically significant elevations in organ weights were noted in males at 60 mg/kg/d and included: (a) increases in absolute heart, kidney, and liver weights; (b) increased liver to body weight ratios; and (c) increased heart, kidney, liver, spleen, and epididymides to brain weight ratios. In females, statistically significant increases in organ weights were limited to increases in adrenal to brain weights at ≥10 mg/kg/d, kidney to brain weights at ≥30 mg/kg/d, and kidney to body weight and liver to brain weight ratios at 60 mg/kg/d. There were no macroscopic or microscopic pathology changes observed in any of the tissues examined. Importantly, light microscopic examination of the kidney was unremarkable at the end of the 2-wk dosing period with n-butyl maleate. Although lacking a histopathological correlate, resultant increases in organ weights at 60 mg/kg/d might be considered indicative of an adverse effect. However, renal perturbation induced by n-butyl maleate was mild in comparison to maleic acid-induced renal toxicity, which manifested as impaired tubular resorption and necrosis of the proximal tubules at doses ≥60 mg/kg/d. The no-observed-adverse-effect level (NOAEL) for the study was 30 mg/kg/d.

Postnatal development of rat pups after maternal exposure to diethanolamine

Diethanolamine (DEA), a widely used surfactant, was administered to pregnant mice at the oral LD10 resulting in failure of pups to grow and thrive through postnatal day (PND) 3 [National Toxicology Program, 1987; York et al., Teratology 37:503-504, 1988]. The toxicity profile for DEA differs among rodent species. This study investigated DEA-induced postnatal toxicity in a second species. Timed-mated Sprague-Dawley rats were dosed (0, 50, 125, 200, 250, or 300 mg DEA/kg/day, p.o.) on gestational days (GD) 6-19. Dams and pups were monitored for body weight, feed/water intake, clinical signs, litter size, and sex ratio. At necropsy (PND 21), maternal liver and kidney weights and number of uterine implantation sites were recorded. The high-dose group was terminated early due to excessive toxicity. The estimated maternal LD10 was 218 mg/kg/day. Maternal effects included decreased body weight and relative feed intake (>or=200 mg/kg/day), transiently reduced relative water intake (125 and 250 mg/kg/day), and increased absolute kidney weight (>or=125 mg/kg/day). Postimplantation loss (PND 0) and pup mortality (PND 0-4) were increased (>or=200 and >or=125 mg/kg/day, respectively). Pup body weight was reduced (>or=200 mg/kg/day) as late as PND 21. This study demonstrates reduced postnatal growth and survival in a second species after gestational exposure to DEA, persistence of toxic effects through the end of lactation, possibly due to long elimination half-life, and maternal and developmental toxicity no-observed-adverse-effect level (NOAELs) (50 mg/kg/day) and lowest-observed-adverse-effect level (LOAELs) (125 mg/kg/day) for oral DEA exposure during embryo/fetal development in the rat.

Lack of carcinogenicity of d-xylose given in the diet to F344 rats for two years

The two year carcinogenicity of d-xylose was examined in groups of 50 male and 50 female F344 rats at dietary doses of 0% (control), 2.5% and 5%. The doses were selected on the basis of results from a 13-week subchronic toxicity study. Growth suppression and soft feces were observed in male and female rats of the 5% group. However, no significant differences from the controls were noted with regard to clinical signs, mortality and hematological findings. Decrease in absolute weight and increase in relative weight of the brain in males, and decrease of absolute kidney weight in females were observed in the 5% group, but there were no remarkable histopathological changes. A variety of tumors developed in all groups, including the controls, but all were histologically similar to those known to occur spontaneously in F344 rats, and no statistically significant increase in the incidence of any type of neoplastic lesion was found for either sex in the treated groups. Thus, it was concluded that, under the present experimental conditions, d-xylose is not carcinogenic to F344 rats.

Attenuating effect of soy protein as compared with casein on glomerular injury in spontaneous hypercholesterolemic male Imai rats

SUMMARY: Soy protein has hypocholesterolemic and oestrogenic properties. Because the reno‐protective effect of both lipid‐lowering agents and oestrogen has been reported, we investigated whether soy protein has an ability to attenuate glomerular injury in male Imai rats in which hyperc‐holesterolemia, focal and segmental glomerulosclerosis (FSGS) and renal insufficiency occur spontaneously. Twenty male Imai rats were randomly divided into two groups and fed diets containing 20.0 g/100 g of either casein or soy protein. Each group was fed freely one of the respective test diets from when they were 8–26 weeks of age. Bodyweight, urinary protein, serum constituents and systolic blood pressure was investigated every 4 or 8 weeks from when rats were 10 weeks through to 26 weeks of age. At 26 weeks of age, rats were studied morphologically. Soy protein‐fed animals consumed larger amounts of diet and showed higher urinary urea excretion and a more rapid weight gain than the control casein diet‐fed animals. No significant differences were seen in blood pressure between the two groups. the soy protein diet did not influence absolute kidney or heart weight, but significantly reduced those organs to bodyweight ratios. Soy protein diet resulted in less proteinuria, less hyperlipidemia, less hypoalbuminemia, less renal functional impairment, less glomerular hypertrophy, and less renal histological damage as compared with the control casein diet. the soy protein diet tended to affect serum sex‐hormone levels with a trend toward lower levels of both testosterone and estradiol. the present study showed a beneficial effect of soy protein diet on glomerular disease in a spontaneous FSGS model, although the mechanisms remain to be determined.