Kidney Of Female Wistar Rats Research Articles

Histopathological effect of Buccholzia coricea on some liver and kidneys in alloxan-induced diabetic Wistar rats

Liver and kidneys are vital organs that play several important roles such as detoxification, storage of blood, blood filtration and purification, urine excretion and secretion of hormones among others. This study was conducted to determine the histopathological effects of Buccholzia coricea on the liver and kidneys of female wistar rats, Twenty-five female wistar rats were divided into five groups of five rats per group. The five rats in group one served as the normal control group and were fed with food and water without inducement and treatment. Test group two, the positive control were induced with alloxan (150 mg/kg) without any treatment throughout the study. Test group three, the known drug group were induced with diabetes (150 mg/kg) and administered metformin daily. Test group four were induced with diabetes and were treated with low dose of 250 mg/kg of Buccholzia coriacea seed extract daily throughout the study. Test group five were induced with diabetes and were treated with high dose of 1000 mg/kg of Buccholzia coriacea seed extract daily throughout the study for 14 days and the animal models were checked daily with glucometer to ascertain their blood sugar level before the animals were sacrificed and organs harvested and preserved for histological analysis. At the end of the 14 days, hematoxylin and eosin staining methods of histological methods were used. The results of the histology of the five groups showed that group one had normal liver and kidney tissues. Group two showed cytoplasmic vacoulation and cellular infiltration of liver but an inflammation of the kidney tissue. Group three had mild sinusoidal dilation in the liver and distention of the renal tubules with reduced inflammation of the kidney tissue. Group four had cytoplasmic vacoulation of liver and reduced inflammatory activities of the kidney tissue. Group five had mild cellular degeneration of liver, hemorrhage and inflammation of the kidney tissue. Thus, Buccholzia coriacea can improve the functioning of the liver and kidneys of a diabetic rats when it is consumed below 1000mg and its equivalent daily by mitigation of the histopathological alterations by alloxan-induced diabetes. Buccholzia coriacea is a natural panacea in the management of diabetes-related organ damage.

Effects of Graded Doses of Ethanolic Extract of Pausinystalia Yohimbe Stem Bark on Biochemical and Hematological Indices In the Kidneys of Female Wistar Rats

Pausinystalia yohimbe is a medicinal plant widely used as an aphrodisiac agent in Nigeria and other parts of West Africa, but little is known about its effect on renal function after chronic use. This study was designed to investigate the effect of ethanolic extract of Pausinystalia yohimbe stem bark on renal function parameters such as serum creatinine, urea, electrolyte, oxidative stress markers, and hematological parameters in female Wistar rats. Ethanolic extract of Pausinystalia yohimbe stem bark was administered orally to 3 groups of 5 female rats for 21 days as follows: group1 which served as control received distilled water while groups 2 and 3 received 400mg/kg and 800mg/kg body weight of the extract respectively. Thereafter the rats were sacrificed, and blood and kidney tissues were collected for biochemical analysis. The result showed that there were no significant changes in urea, creatinine, potassium, chloride, and bicarbonate levels while sodium level was significantly increased (p<0.05) when compared to the control. SOD and CAT tissue activities did not show any significant change (p<0.05) while there was a significant increase (p<0.05) in GSH and a significant reduction (p<0.05) in MDA. Also, there was no significant change (p<0.05) in WBC, PCV, and platelets, however, there was a significant decrease (p<0.05) in RBC and hemoglobin levels. The histopathology of the kidney showed that no significant changes were observed between treatment groups and control except for the 800 mg/kg body weight of the extract-treated group where there was mild multifocal vacuolar degeneration of some renal tubular epithelial cells. The result suggests that the chronic use of the ethanolic extract of Pausinystalia yohimbe stem bark protects the kidney against oxidative stress but adversely affects the functional capacities of the kidney and formation of erythropoietin in the stem cells and may also contribute to the increasing number of persons with high blood pressure.

Toxicity of Acephate to Liver and Kidney of Female Wistar Rats

Acephate is a broad spectrum insecticide used against pests of vegetables, cotton and ornamental plants. In the present study, acephate was orally administered to female wistar rats to examine its toxic effects, if any, at dose level of 1/50th, 1/25th and 1/10th of LD50 value along with a control group for 45 days. Results revealed a remarkable decrease in the feed intake of 1/10th acephate treated rats during 5th and 6th week of treatment. The net body weights and liver weight decreased non-significantly to a small extent over 45 days of treatment. The weight of kidney and content of total soluble protein decreased significantly in a dose dependent manner in treated rats. The significant alterations in the activity of antioxidative enzymes i.e. glutathione peroxidase, glutathione-S-transferase, glutathione reductase, superoxide dismutase, catalase and lipid peroxidation levels were observed. The appearance of comet in 1/10th dosed rats indicated DNA damage. Further, no formation of concentric rings in treated rats indicated the absence or low concentration of antibodies in the serum.

Intraperitoneal injections of copper ferrite nanoparticles disturb blood, plasma, and antioxidant parameters of Wistar rats in a sex-specific manner.

The present study was designed to report the synthesis and characterization of copper ferrite nanoparticles (CF NPs) and their biocompatibility in Wistar rats. Coprecipitation method was used to generate CF NPs having average diameter of 14.06 nm. NPs were characterized by scanning electron microscopy and X-ray diffraction. Six-week-old Wistar rats of both sexes intraperitoneally received 10 mg/ml saline/Kg body weight of CF NPs for 14 days. Control groups were maintained in parallel that received saline solution for 14 days through same route. Open field and novel object recognition tests, complete blood count, selected plasma parameters, antioxidants, and copper concentration in vital organs were determined in all treatments. Female rats treated with CF NPs had significantly higher platelet count (P = 0.05) and platelet crit (P = 0.05) and decreased plasma triglyceride concentration levels (P = 0.02) than control group. Female rats had significantly increased levels of superoxide dismutase (P = 0.01), catalase (P = 0.05), and malonaldehyde (P = 0.05) in the kidney, while male rats had significantly elevated levels of superoxide dismutase in the lungs (P = 0.01) as compared with respective control groups. Copper concentrations in the liver were significantly higher in both female (P = 0.04) and male (P = 0.05) rats exposed to CF NPs than control group. All other studied parameters of behavioral tests, blood biochemistry, antioxidant, and copper concentrations in the brain varied nonsignificantly (P > 0.05) when compared between CF NPs treated and untreated rats of both sexes. Intraperitoneal supplementation of CF NPs for 14 days disturbed the platelet count, plasma triglyceride concentration, copper levels in the liver, and antioxidant concentrations in the kidney of female Wistar rats. These parameters remained unaffected in male subjects.

Oral subchronic exposure to silver nanoparticles causes renal damage through apoptotic impairment and necrotic cell death

Silver nanoparticles (AgNPs) are one of the most widely used nanomaterials. Following oral exposure, AgNPs can accumulate in various organs including kidneys where they show gender specific accumulation. There is limited information on their effect on renal system following long-term animal exposure especially at the ultramicroscopic and molecular level. In this study, we have assessed the effect of 60 days oral AgNPs treatment on kidneys of female Wistar rats at doses of 50 ppm and 200 ppm that are below previously reported lowest observed adverse effect level (LOAEL). AgNPs treatment led to decrease in kidney weight and some loss of renal function as seen by increased levels of serum creatinine and early toxicity markers such as KIM-1, clusterin and osteopontin. We also observed significant mitochondrial damage, loss of brush border membranes, pronounced swelling of podocytes and degeneration of their foot processes using transmission electron microscopy (TEM). These symptoms are similar to those seen in nephrotic syndrome and ‘Minimal change disease’ of kidney where few changes are visible under light microscopy but significant ultrastructural damage is observed. Prolonged treatment of AgNPs also led to the activation of cell proliferative, survival and proinflammatory factors (Akt/mTOR, JNK/Stat and Erk/NF-κB pathways and IL1β, MIP2, IFN-γ, TNF-α and RANTES) and dysfunction of normal apoptotic pathway. Our study shows how long term AgNPs exposure may promote ultrastructural damage to kidney causing inflammation and expression of cell survival factors. These changes, in the long term, could lead to inhibition of the beneficial apoptotic pathway and promotion of necrotic cell death in kidneys.

The influence of exposure to immunosuppressive treatment during pregnancy on renal function and rate of apoptosis in native kidneys of female Wistar rats

Pregnancy puts a significant additional strain on kidneys. The aim of our study was to investigate the impact of immunosuppressive drugs on changes in native kidneys in female Wistar rats after exposure during pregnancy. The study was conducted on 32 dams, subjected to immunosuppressive regimens commonly used in the therapy of human kidney transplant recipients (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; cyclosporine A, everolimus and prednisone). The animals received drugs for 2 weeks before pregnancy and during 3 weeks of pregnancy. In all treated dams lower body weight (but not kidney mass) and alterations in serum sodium and chloride ions were found; serum creatinine concentration was increased in dams treated with cyclosporine A, everolimus and prednisone. All treatment groups of dams showed increased apoptosis in the distal tubules. In histological examination the changed intensity of acidophilic or basophilic cytoplasm of epithelial cells was found in kidneys of rats treated with calcineurin inhibitors, mycophenolate mofetil and prednisone. All immunosuppressive regimens caused abnormalities affecting nephron tubules. Regimens containing calcineurin inhibitors and mycophenolate mofetil caused higher rate of apoptosis and more pronounced histopathological changes. Regimen based on everolimus despite the lower rate of apoptosis in the proximal tubules and lower accumulation of kidney injury markers revealed higher serum creatinine concentration. Thus, interpretation which combination of drugs is better or worse for long-lasting functioning of kidneys in pregnant females requires further studies.

In vitro and in silico study of antioxidant effect of Bergenia ciliata and Terminalia chebula against sodium oxalate induced oxidative stress

Previous experimental evidence suggested that Bergenia ciliata (Saxifragaceae) and Terminalia chebula Retzius(Combretaceae) are effective against nephrolithiasis and have potential antioxidant activity. In this regard, hydro-methanolic extracts of B. ciliata rhizomes and T. chebula fruits were investigated for antioxidant potential against sodium oxalate induced oxidative imbalance in the kidney of female Wistar rats. We also performed molecular docking studies of all the reported phenolic compounds of both the plants to evaluate its interaction with the active site of oxalate binding protein (OBP). In summary, our findings showed that sodium oxalate caused significant increase in lipid peroxidation with concurrent decrease in activities of superoxide dismutase and catalase as well as in total reduced glutathione content in a concentration-dependent manner. The hydro-alcoholic extracts, however, when co-administered with sodium oxalate resulted in significant protection with maximum percent protection was achieved by B. ciliata. Thereafter, daucosterol showed best binding efficiency with OBP. However, further work on the purification of isolated bioactive components and pharmacological testing can reveal the therapeutic potential of the plant.

Toxicological Evaluations of the Crude Extracts and Fractions of Moringa stenopetala Leaves in Liver and Kidney of Rats

Background: Moringa stenopetala is a medicinal plant that has been used in Ethiopian tradi-tional medicine as a remedy for treatment of hypertension, diabetes, malaria and stomach pain. Objective: The aim of this study was to assess the safety of the extracts and fractions of Moringa stenopetala leaves in liver and kidney of female Wistar rats. Methods: For acute toxicity study, the female Wistar rats were randomly divided into control and treatment groups that received distilled water and oral administration of single dose of 5000 mg/kg (n=5) extract, respectively and followed for 14 days. For repeated daily administration of extract, the female Wistar rats were Female Wistar rats were randomly divided into control and treatment groups (n=6). Treatment groups were given daily extracts (250, 500, and 1000 mg/kg) orally. Whereas, normal control received distilled water ad libitum for 15 days. On the 16th day the blood was sampled to evaluate the effect on liver and kidney using clinical chemistry analyzer. Results: The acute toxicity study found no signs of toxicity; hence LD50 was greater than 5000 mg/kg. The biochemical test revealed that extracts produced a rise in liver in a dose de-pendent manner but no effect on kidney function indicators compared with normal control. Conclusion: These findings revealed that the extracts of Moringa stenopetala are toxic to liver but not to kidney.

Polyphenolic extract of Piper nigrum inhibits sodium oxalate induced oxidative stress in rat kidney

Natural antioxidants can be therapeutic agents for the prevention and treatment of nephrolithiasis because of the presence of phyto-compounds. Polyphenolic extract of Piper nigrum (Piperaceae) fruits, was investigated for antioxidant potential against sodium oxalate induced oxidative imbalance. The results were also compared with a standard polyherbal drug for nephrolithiasis, cystone. The kidney of female Wistar rats treated with sodium oxalate at different concentrations showed significant increase in lipid peroxidation (208–619%) and decrease in activities of superoxide dismutase (82–25%) and catalase (88–37%). Furthermore, sodium oxalate also caused decrease in reduced glutathione content in rat kidney (84–35%). However, the co-incubation of extract and sodium oxalate showed significant protection in concentration-dependent manner. The results of the present study concluded that P. nigrum can be used in neutraceuticals and food industry for antioxidant activity, however, further detailed studies at the cellular level are needed.

Oxidative stress in the kidney of reproductive female rats during aging

Reproduction is a costly life process, and the reproductive investment by females appears to be greater than males in many species. We have analyzed the effects of reproductive investment during aging with respect to oxidative stress parameters in female Wistar rats. We measured the activity glutathione peroxidase, glutathione S-transferase, superoxide dismutase, consumption of hydrogen peroxide, protein carbonylation, lipid peroxidation, nitrite and nitrate levels, and Vitamin C (Vit. C) and E levels. We traced oxidative profiles at ages 3, 6, 12, and 24 months. Animals were grouped according to reproductive experience: experienced or naive with respect to reproductive activity. We measured aconitase activity and sex hormone levels. The naive animals exhibited an increase with respect to experienced in most parameters studied at 6 and 24 months, whereas experienced animals exhibited a similar increase at 3 and 12 months. At 6 months of age, during the period that would represent peak reproductive activity, naive animals showed higher levels of MDA, Vit. C, consumption of hydrogen peroxide and GPx, aconitase, and SOD activities. In naive elderly rats, we observed an increase in oxidative damage markers and an increase in enzymatic and non-enzymatic antioxidants, with the exception of consumption of hydrogen peroxide and Vit. C. In the long term, the reproductive investment was not sufficient to interfere with antioxidant capacity, and did not contribute to oxidative damage in kidneys of female Wistar rats.

Toxicological effects of phosphide powder residue in female rats

Background: Fumigation of cowpea (Vigna unguiculata L. Walp.) using aluminium phosphide is a common practice and contact with this chemical has been demonstrated to result in organ damage, but there is dearth of data on the impact of its powder residue on a mammalian species. Aims & Objective: The aim of this study is to determine the effect of post-fumigation residue on both liver and kidney of female Wistar rats. Material and Methods: Eighteen rats were randomly divided into each of the three experimental groups. A group was fed with untreated cowpea and served as control; either of the two other groups was fed phosphide-powder residue contaminated or uncontaminated cowpea. Serum obtained from blood that was collected through retro-orbital bleeding was utilized for biochemical analysis. Results: While contact with treated but uncontaminated cowpea did not result in either hepatic or renal damage, rats fed phosphide-residue contaminated cowpea exhibited both hepatic and renal damage as the indices (alanine & aspartate aminotransferases, γ- glutamyl transferase, alkaline phosphatase, total protein, albumin, urea, uric acid, creatinine) of study were significantly different (p

Activating Nrf-2 Signaling Depresses Unilateral Ureteral Obstruction-Evoked Mitochondrial Stress-Related Autophagy, Apoptosis and Pyroptosis in Kidney

Exacerbated oxidative stress and inflammation may induce three types of programmed cell death, autophagy, apoptosis and pyroptosis in unilateral ureteral obstruction (UUO) kidney. Sulforaphane activating NF-E2-related nuclear factor erythroid-2 (Nrf-2) signaling may ameliorate UUO-induced renal damage. UUO was induced in the left kidney of female Wistar rats. The level of renal blood flow, cortical and medullary oxygen tension and reactive oxygen species (ROS) was evaluated. Fibrosis, ED-1 (macrophage/monocyte) infiltration, oxidative stress, autophagy, apoptosis and pyroptosis were evaluated by immunohistochemistry and Western blot in UUO kidneys. Effects of sulforaphane, an Nrf-2 activator, on Nrf-2- and mitochondrial stress-related proteins and renal injury were examined. UUO decreased renal blood flow and oxygen tension and increased renal ROS, 3-nitrotyrosine stain, ED-1 infiltration and fibrosis. Enhanced renal tubular Beclin-1 expression started at 4 h UUO and further enhanced at 3d UUO, whereas increased Atg-5-Atg12 and LC3-II expression were found at 3d UUO. Increased renal Bax/Bcl-2 ratio, caspase 3 and PARP fragments, apoptosis formation associated with increased caspase 1 and IL-1β expression for pyroptosis formation were started from 3d UUO. UUO reduced nuclear Nrf-2 translocation, increased cytosolic and inhibitory Nrf-2 expression, increased cytosolic Bax translocation to mitochondrial and enhanced mitochondrial Cytochrome c release into cytosol of the UUO kidneys. Sulforaphane significantly increased nuclear Nrf-2 translocation and decreased mitochondrial Bax translocation and Cytochrome c release into cytosol resulting in decreased renal injury. In conclusion, sulforaphane via activating Nrf-2 signaling preserved mitochondrial function and suppressed UUO-induced renal oxidative stress, inflammation, fibrosis, autophagy, apoptosis and pyroptosis.

Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats.

The cofactor nicotinamide adenine dinucleotide (NAD+) has emerged as a key regulator of metabolism, stress resistance and longevity. Apart from its role as an important redox carrier, NAD+ also serves as the sole substrate for NAD-dependent enzymes, including poly(ADP-ribose) polymerase (PARP), an important DNA nick sensor, and NAD-dependent histone deacetylases, Sirtuins which play an important role in a wide variety of processes, including senescence, apoptosis, differentiation, and aging. We examined the effect of aging on intracellular NAD+ metabolism in the whole heart, lung, liver and kidney of female wistar rats. Our results are the first to show a significant decline in intracellular NAD+ levels and NAD∶NADH ratio in all organs by middle age (i.e.12 months) compared to young (i.e. 3 month old) rats. These changes in [NAD(H)] occurred in parallel with an increase in lipid peroxidation and protein carbonyls (o- and m- tyrosine) formation and decline in total antioxidant capacity in these organs. An age dependent increase in DNA damage (phosphorylated H2AX) was also observed in these same organs. Decreased Sirt1 activity and increased acetylated p53 were observed in organ tissues in parallel with the drop in NAD+ and moderate over-expression of Sirt1 protein. Reduced mitochondrial activity of complex I–IV was also observed in aging animals, impacting both redox status and ATP production. The strong positive correlation observed between DNA damage associated NAD+ depletion and Sirt1 activity suggests that adequate NAD+ concentrations may be an important longevity assurance factor.

Estrogen modulates ClC-2 chloride channel gene expression in rat kidney.

ClC-2 is a CLC family member of chloride channels sensitive to changes in cell volume, pH and voltage. The ClC-2 is widely distributed along the nephron although in the kidney its role still not well understood. Aldosterone studies suggest that ClC-2 expression in the kidney may be hormonally regulated. To explore the possibility that estrogen control ClC-2 expression, we investigated whether its expression changed in the kidney of female Wistar rats subjected to ovariectomy with or without near-physiological or high doses of 17beta-estradiol benzoate treatment for 10 days. Total RNA isolated from rat kidney and dissected nephron segments was analyzed by ribonuclease protection assay and/or a semi-quantitative RT-PCR. The renal ClC-2 protein expression was analyzed by Western blot. The decreased renal expression of ClC-2 mRNA and protein observed in ovariectomized rats was restored to control levels after treatment with low doses of estradiol. Higher dose estradiol lead to an even greater increase in ClC-2 mRNA and protein expression. This change in overall expression was shown to be caused by the modulation of ClC-2 mRNA expression in the proximal tubule. These results suggest that ClC-2 may be involved in estrogen-induced Cl(-) transport in rat kidney.