Renal Cortical Tubules Research Articles

Molecular mechanism of NR4A1/MDM2/P53 signaling pathway regulation inducing ferroptosis in renal tubular epithelial cells involved in the progression of renal ischemia-reperfusion injury

Revealing the possible molecular mechanism of the NR4A1 (nuclear receptor subfamily 4 group A member 1)-MDM2 (MDM2 proto-oncogene)-P53 (tumor protein p53) signaling pathway that induces ferroptosis in renal tubular epithelial cells. Renal ischemia-reperfusion injury (RIRI) -related datasets were obtained from the GEO database. Differentially expressed genes in RIRI were analyzed using R language, intersected with RIRI-related genes in the GeneCard database, and retrieved from the literature to finally obtain differential ferroptosis-related genes. An in vitro cell model of RIRI was constructed using mouse renal cortical proximal tubule epithelial cells (mRTEC cells) treated with hypoxia-reoxygenation (H/R). Bioinformatic analysis showed that NR4A1 may be involved in RIRI through the induction of ferroptosis; in addition, we predicted through online databases that the downstream target gene of NR4A1, MDM2, could be targeted and regulated by ChIP and dual luciferase assays, and that NR4A1 could prevent MDM2 by inhibiting it, and NR4A1 was able to promote ferroptosis by inhibiting the ubiquitinated degradation of P53. NR4A1 expression was significantly increased in mRTEC cells in the hypoxia/reoxygenation model, and the expression of ferroptosis-related genes was increased in vitro experiments. NR4A1 reduces the ubiquitinated degradation of P53 by targeting the inhibition of MDM2 expression, thereby inducing ferroptosis and ultimately exacerbating RIRI by affecting the oxidative respiration process in mitochondria and producing oxidized lipids. This study presents a novel therapeutic approach for the clinical treatment of renal ischemia-reperfusion injury by developing drugs that inhibit NR4A1 to alleviate kidney damage caused by renal ischemia-reperfusion.

Ameliorative Effects of Alpha-tocopherol in Carboplatin Induced Toxicity on Histomorphology of Renal Cortex in Rats.

To evaluate the histomorphological response of alpha-tocopherol co-administration with carboplatin chemotherapy. A laboratory-based experimental study. Place and Duration of the Study: Anatomy Department, Army Medical College / National University of Medical Sciences (NUMS), Rawalpindi, Pakistan, from January to December 2021. Thirty adult Sprague-Dawley rats were divided into three groups of ten rats each. Control group A received normal diet and water, experimental group B was administered single injection of carboplatin 2.5 mg/Kg intraperitoneally; and experimental group C along with carboplatin injection also received alpha-tocopherol 62.7 mg/Kg daily. At the end of 12 weeks, the euthanasia of animals was done and kidneys were dissected out. Right-sided kidneys were stained with Haematoxylin and Eosin. Micrometry was done to measure the diameters of renal cortical tubules and renal corpuscles. The proximal and distal tubular and luminal diameter and transvertical diameter of renal corpuscle were increased in group B as compared to control group A. In group C, the proximal and distal tubular diameters were 5.175 ± 0.39 µm and 3.88 ± 0.364 µm, respectively; proximal and distal luminal diameters were 2.67 ± 0.35 µm and 1.64 ± 0.24 µm, respectively and transvertical diameter of renal corpuscle was 12.16 ± 0.870 µm. These values were less than experimental group B and closer to that of control group A. Renal microscopic parameters showed improvement in the group administered with alpha-tocopherol. Therefore, alpha-tocopherol has ameliorative effects on carboplatin-induced renal damage. Alpha-tocopherol, Carboplatin, Renal corpuscle, Tubules.

A 90-day dose toxicity study of 2-(2H-benzotriazol-2-yl)-6-dodecyl-4-methylphenol in rats

2-(2H-benzotriazol-2-yl)-6-dodecyl-4-methylphenol (BTMLP, CAS No. 125304-04-3) is widely used as a liquid ultraviolet absorber that prevents deterioration of synthetic resins and so on. To investigate its toxicological properties and determine the no-observed-adverse-effect level (NOAEL), a 90-day repeated oral toxicological study of BTMLP was conducted in Crl:CD (SD) rats at doses of 0 (vehicle control, corn oil), 100, 300, and 1000 mg/kg/day. There was no observed mortality or abnormal clinical signs related to the treatment of any group. Body weight and food consumption were not affected by BTMLP treatment. In males, significant prolongations of prothrombin time and activated partial thrombin time were observed in the BTMLP-treated groups. Histopathological examination revealed a slight increase of the eosinophilic bodies and hyaline droplets in the renal cortical tubules in the 1000 mg/kg group in males. As mentioned above, the toxic effect of the BTMLP was noted in the blood coagulation system and kidneys only in males. Based on these findings, the NOAEL was judged to be less than 100 mg/kg/day in males and 1000 mg/kg/day in females under this study’s condition.

Amelioration of Carboplatin-Induced Changes in Rat Renal Cortical Tubulesby Alpha-Tocopherol

Objective: To determine the effects of carboplatin and alpha-tocopherol co-administration on gross kidney features and renal cortical tubules of carboplatin-treated rats.
 Study Design: Laboratory-based experimental study.
 Place and Duration of Study: Department of Anatomy, Army Medical College/National University of Medical Sciences Rawalpindi Pakistan, in collaboration with the National Institute of Health (NIH) and Pathology Lab Pak Emirates Rawalpindi Pakistan, from Jan to Dec, 2021.
 Methodology: Thirty adults "Sprague-Dawley rats" of both genders were used and were divided into three Groups. Group-A was the Control Group. Groups B and C were given injection carboplatin 2.5 mg/kg body weight intraperitoneally on the first day. Group-C was given vitamin E at a dose of 62.7 mg/kg body weight daily via oral gavage starting from the second day of the experiment till the end of 12 weeks. Rats were euthanized at the end, kidneys were dissected, and they were preserved in 10% formalin after gross inspection. Tissue processing and staining were performed. A microscopic study was done to observe proximal and distal tubule necrosis.
 Results: Thirty adult Sprague Dawley rats, of age 10-12 weeks, and weight 250.0±50.0 grams, were included, there was statistically significant difference in the animal weight difference (p=0.001), length of right kidneys (cm) (p=0.002), width of right kidney (cm) (p= 0.001) and weight of right kidney (gm) (p=0.012) kidneys and relative tissue body weight index (RTBWI) (p = 0.048) of Control Group-A and Experimental Group B and C.
 Conclusion: Alpha-tocopherol has an ameliorative effect on gross features of rat kidneys..........

The possible protective role of vitamin E against deferasirox-induced injury of renal cortical tubules in adult male albino rat: A histological and immunohistochemical study

The possible protective role of vitamin E against deferasirox-induced injury of renal cortical tubules in adult male albino rat: A histological and immunohistochemical study

Ameliorative role of alpha-lipoic acid in renal cortical structural damage, induced by limb ischemia-reperfusion injury in the rat

ABSTRACT Ischemia-reperfusion injury is related to kidney dysfunction due to bilateral lower limb ischemia. This kidney injury may lead to acute kidney failure and mortality. Alpha-Lipoic Acid, a known antioxidant, can ameliorate kidney dysfunction and histopathology related to several etiologies. Ischemia was performed in adult male rats by bilateral femoral artery occlusion, then ischemia-reperfusion was done for 1 day and 7 days. Lipoic acid was administered to rats that had undergone ischemia-reperfusion for 7 days. The renal cortices of the kidneys of the tested groups were processed for light and electron microscopic examination. Immunohistochemical evaluation was performed using the following markers: cleaved caspase 3, inducible nitric oxide synthase, and tumor necrosis factor-alpha. There was damage to the renal cortical tubules and degeneration of podocytes and thickening of the glomerular basement membrane. Additionally, there was an increase in apoptosis and the inflammatory markers’ immunoreactivity. Administration of alpha-lipoic acid resulted in improvement of the structural and immunohistochemical changes of the renal cortex. This may suggest a therapeutic rule of it and promising application for variable kidney injuries.

Renal AT2 Receptors Mediate Natriuresis via Protein Phosphatase PP2A.

How signals from activated angiotensin type-2 receptors (AT2R) mediate inhibition of sodium ion (Na+) reabsorption in renal proximal tubule cells is currently unknown. Protein phosphatases including PP2A (protein phosphatase 2A) have been implicated in AT2R signaling in tissues other than kidney. We investigated whether inhibition of protein phosphatase PP2A reduced AT2R-mediated natriuresis and evaluated changes in PP2A activity and localization after renal AT2R activation in normal 4- and 10-week-old control Wistar-Kyoto rats and 4-week-old prehypertensive and 10-week-old hypertensive spontaneously hypertensive rats. In Wistar-Kyoto rats, direct renal interstitial administration of selective AT2R nonpeptide agonist Compound-21 (C-21) increased renal interstitial cyclic GMP (cGMP) levels, urine Na+ excretion, and simultaneously increased PP2A activity ≈2-fold in homogenates of renal cortical tubules. The cyclic GMP and natriuretic responses were abolished by concurrent renal interstitial administration of protein phosphatase inhibitor calyculin A. In renal proximal tubule cells in response to C-21, PP2A subunits A, B55α and C, but not B56γ, were recruited to apical plasma membranes together with AT2Rs. Calyculin A treatment abolished C-21-induced translocation of both AT2R and PP2A regulatory subunit B55α to apical plasma membranes. Immunoprecipitation of AT2R solubilized from renal cortical homogenates demonstrated physical association of AT2R with PP2A A, B55α, and C but not B56γ subunits. In contrast, in spontaneously hypertensive rats, administration of C-21 did not alter urine Na+ excretion or PP2A activity and failed to translocate AT2Rs and PP2A subunits to apical plasma membranes. In renal proximal tubule cells of Wistar-Kyoto rats, PP2A is activated and PP2A subunits AB55αC are recruited to C-21-activated AT2Rs during induction of natriuresis. This response is defective in prehypertensive and hypertensive spontaneously hypertensive rats, presenting a potential novel therapeutic target for treating renal Na+ retention and hypertension.

Identification of multinucleated cells in human kidney cortex: A way for tissue repairing?

The presence of multinucleated cells has never been demonstrated in renal tissue, although, polyploid cells were recently observed in the tubules of normal and pathological human kidney. Therefore, the aim of the present study is to identify and quantify, by electron microscopy, multinucleated cells in the cortical tissue of normal human kidney i.e., in the three compartments of renal tubule: the proximal tubule (PT), the distal tubule (DT), and the collecting duct (CD), as well as, in the glomerulus (podocytes). The percentage of the multinucleated cells observed was 5% (95%CI: 3.6%–6.7%) in renal cortical tubules with distribution in each tubular compartment of 6% in PT, 4% in DT and 3% in CD with no statistically significant difference in the distribution of multinucleated cells according to tubular compartments. Four percent of analysed podocytes (in total 149 podocytes) were multinucleated (95%CI: 1.5%−8.6%). In conclusion, multinucleated cells were identified and quantified in functionally normal kidneys, as previously demonstrated in other organs such as the liver.

Therapeutic role of Azadirachta indica leaves ethanolic extract against diabetic nephropathy in rats neonatally induced by streptozotocin

ABSTRACT Diabetic nephropathy (DN) is manifested by chronic loss of renal function due to damage of glomeruli and renal tubules. Therefore, this study is mainly designed to evaluate the therapeutic role of Azadiracta indica (neem) leaves extract as a novel approach for treatment of DN in rats neonatally induced by streptozotocin (STZ). For this study, 40 offspring were selected after parturition and categorized into four groups (n = 10). Group1: control group, group 2: neem leaves extract supplemented group, group 3: diabetic group that injected with a single dose of STZ and group 4: diabetic group treated with neem extract. The results revealed deleterious histological and ultrstructural changes in the renal tissues of diabetic rats. Such changes included atrophied glomeruli, dilated renal cortical tubules and scattered hemorrhage spots, thickening of glomerular basement membrane, expansion of mesangial matrix and pyknotic podocyte. Additionally, the proximal convoluted tubule and distal tubule showed cytoplasmic vacuolation, vacuolated mitochondria, scattered lipid droplets, lost microvilli and disrupted basal lamina and basal infoldings. Moreover, significant decreased levels of serum antioxidants (SOD&CAT) and significant increased levels of serum MDA, urea and creatinine were noticed in diabetic rats. Neem leaves extract successfully alleviated the histological and ultrastructural as well as biochemical changes induced by diabetes.

MHC class II in renal tubules plays an essential role in renal fibrosis.

Immunomodulation is considered a potential therapeutic approach for chronic kidney disease (CKD). Although it has been previously reported that CD4+ T cells contribute to the development of renal fibrosis, the role of MHC class II (MHCII) in the development of renal fibrosis remains largely unknown. The present study reports that the expression of MHCII molecules in renal cortical tubules is upregulated in mouse renal fibrosis models generated by unilateral ureter obstruction (UUO) and folic acid (FA). Proximal tubule epithelial cells (PTECs) are functional antigen-presenting cells that promote the proliferation of CD4+ T cells in an MHCII-dependent manner. PTECs from mice with renal fibrosis had a stronger ability to induce T cell proliferation and cytokine production than control cells. Global or renal tubule-specific ablation of H2-Ab1 significantly alleviated renal fibrosis following UUO or FA treatment. Renal expression of profibrotic genes showed a consistent reduction in H2-Ab1 gene-deficient mouse lines. Moreover, there was a marked increase in renal tissue CD4+ T cells after UUO or FA treatment and a significant decrease following renal tubule-specific ablation of H2-Ab1. Furthermore, renal tubule-specific H2-Ab1 gene knockout mice exhibited higher proportions of regulatory T cells (Tregs) and lower proportions of Th2 cells in the UUO- or FA-treated kidneys. Finally, Immunohistochemistry (IHC) studies showed increased renal expression of MHCII and the profibrotic gene α smooth muscle actin (α-SMA) in CKD patients. Together, our human and mouse data demonstrate that renal tubular MHCII plays an important role in the pathogenesis of renal fibrosis.

The Possible Radio Protective Role of Gum Arabic on The Kidney Cortex of Adult Male Albino Rats

Aim of the work: the use of ionizing radiation exposure increases, oxidative stress especially for cancer patients. Therefore, there is a critical need to develop antioxidants that prevent oxidative stress damage. Gum Arabic is an antioxidant and anti-inflammatory mediator. This study aimed to assess the possible radio protective effect of gum Arabic (Acacia senegal) against gamma irradiation-induced injury on the rat kidney. Materials and Methods: four groups of male Albino rats (each of 12 rats) received normal saline (G1), dose 5Gy of gamma irradiation (G2), orally administered with 25 mg/kg gum Arabic for 3 weeks (G3) and gamma irradiation plus oral gum Arabic administration for 7 days before and 21 days after irradiation (G4). Results: in the gamma irradiated group, histopathological and ultrastructural examinations of the rat kidney cortical tissue revealed signs of degeneration to the cortical renal tubules and glomeruli. In contrast, gum Arabic treatment alleviated most of the damaging effects of gamma radiation. Conclusion: oral administration of gum Arabic could ameliorate adverse gamma radiation-induced effects that might be attributed to its antioxidative and free radical scavenging effects.

Quantitative and Histological Study of the Effect of Cadmium Oxide on Both Body and Kidney of Mice

The present study was conducted using 24 normal male of Swiss white mice weighing (36-40 gm), 70 days old .The mice were divided into four groups of six mice each. The mice of control group were fed pellet and given tap water during the entire period of the experiment (30 days).The other three groups of mice were given cadmium oxide orally at doses of (7.0 mg / kg body wt., 14.1 mg / kg body wt., and 22.3 mg / kg body wt.) consecutively every day for 30 days and weight in gm was taken once a week. With standard histological techniques, samples were obtained from kidney of the mice. The body weights along with kidney weights were decreased with increase of doses. Also it has been concluded that cadmium oxide caused damages in renal corpuscle (Bowman’s capsule and glomerulus) and renal cortical tubules as well as decrease in body weight and kidney weight (wt.).

Study the Histopathological Effects of Sildenafil Treatment on the Kidney of Adult Male Rats

The present study was aimed to detection the histopathological changes on the kidney of male rats treated with sildenafil drug. In this study, 40 adult male rats were used. These rats divided into four equal groups, each group involved ten rats, group I receive normal saline (1ml/Kg) as control group (N= 10). Group II, III and group IIII was received sildenafil orally at a with following concentration of (1.25,2.5 and 5mg/kg) body weight for 3 months respectively. At the end of experiments. All animals are euthanized and both kidney samples are collected for histopathology assessment. The result demonstrate deferent lesion in kidney structures in treated groups involved degeneration and necrosis of cortical renal tubules, Area of cystic dilation in glomeruli. Cystic dilation in renal tubules also the result recorded dilation glomeruli with dilation of bowman space, finally dilation glomeruli’s with degenerate cellularity and calcification of tubules in compared to control group including normal glomeruli and normal renal tubules.

Urinary TCP1-eta: A Cortical Damage Marker for the Pathophysiological Diagnosis and Prognosis of Acute Kidney Injury.

Acute kidney injury (AKI) is a serious syndrome with increasing incidence and health consequences, and high mortality rate among critically ill patients. Acute kidney injury lacks a unified definition, has ambiguous semantic boundaries, and relies on defective diagnosis. This, in part, is due to the absence of biomarkers substratifying AKI patients into pathophysiological categories based on which prognosis can be assigned and clinical treatment differentiated. For instance, AKI involving acute tubular necrosis (ATN) is expected to have a worse prognosis than prerenal, purely hemodynamic AKI. However, no biomarker has been unambiguously associated with tubular cell death or is able to provide etiological distinction. We used a cell-based system to identify TCP1-eta in the culture medium as a noninvasive marker of damaged renal tubular cells. In rat models of AKI, TCP1-eta was increased in the urine co-relating with renal cortical tubule damage. When kidneys from ATN rats were perfused in situ with Krebs-dextran solution, a portion of the urinary TCP1-eta protein content excreted into urine disappeared, and another portion remained within the urine. These results indicated that TCP1-eta was secreted by tubule cells and was not fully reabsorbed by the damaged tubules, both effects contributing to the increased urinary excretion. Urinary TCP1-eta is found in many etiologically heterogeneous AKI patients, and is statistically higher in patients partially recovered from severe AKI. In conclusion, urinary TCP1-eta poses a potential, substratifying biomarker of renal cortical damage associated with bad prognosis.

Histological Comparative of Kidney of Neonatal Mice Exposed to Silver Nanoparticles During Fetal Development

This study aimed to compare the histological changes in the neonatal kidney after their mothers exposed to different doses of silver nanoparticles colloidal solution (AgNPs) during the three stages of pregnancy. Pregnant Swiss albino mice (n=60) were randomly divided into three treated groups. They were intraperitoneally injected with AgNPs for 7 days during each stage of the gestational period. The newborn mice were sacrificed immediately after the birth, and the kidneys were being collected for histopathological analysis. The results showed that the AgNPs caused histological changes in the neonatal kidneys; vacuolation of some renal vesicles and cortical tubules, cystic tubular dilation, glomerular tuft shrinkage, and focal tubular necrosis in the first week-dose exposed pregnant. Disintegrating of immature glomeruli, distention of Bowman’s space of mature glomeruli, tubular necrosis, loss of renal parenchyma, medullar tubules containing hyaline casts, and subcapsular haemorrhage in the second week-dose exposed pregnant. Massive hypercellularity in the deeper part of the renal cortex, cortical and medullary tubules dilation, atrophy of subcapsular immature tubules, cortical cyst formation, glomerular tuft necrosis, dilation of Bowman’s space with evidence of crescent formation, and medullar portion replaced by scant loose connective tissue containing few numbers of tubules the third week-dose exposed pregnant. The results showed that the AgNPs has more negative effects on the kidney development at the third week-high dose and comparing the histological changes in the neonatal kidney were appeared in a time-depended manner and in a dosedepended manner. More researches must be carried out to obtain better understanding of AgNPs toxicity on fetal development and its ability as a teratogenic agent to induce external and internal abnormalities in the fetus.

Cylindrospermopsin toxicity in mice following a 90-d oral exposure

ABSTRACTCylindrospermopsin (CYN) is a toxin associated with numerous species of freshwater cyanobacteria throughout the world. It is postulated to have caused an episode of serious illnesses in Australia through treated drinking water, as well as lethal effects in livestock exposed to water from farm ponds. Toxicity included effects indicative of both hepatic and renal dysfunction. In humans, symptoms progressed from initial hepatomegaly, vomiting, and malaise to acidosis and hypokalemia, bloody diarrhea, and hyperemia in mucous membranes. Laboratory animal studies predominantly involved the intraperitoneal (i.p.) route of administration and confirmed this pattern of toxicity with changes in liver enzyme activities and histopathology consistent with hepatic injury and adverse renal effects. The aim of this study was designed to assess subchronic oral exposure (90 d) of purified CYN from 75 to 300 µg/kg/d in mouse. At the end of the dosing period, examinations of animals noted (1) elevated organ to body weight ratios of liver and kidney at all dose levels, (2) treatment-related increases in serum alanine aminotransferase (ALT) activity, (3) decreased blood urea nitrogen (BUN) and cholesterol concentrations in males, and (4) elevated monocyte counts in both genders. Histopathological alterations included hepatocellular hypertrophy and cord disruption in the liver, as well as renal cellular hypertrophy, tubule dilation, and cortical tubule lesions that were more prominent in males. A series of genes were differentially expressed including Bax (apoptosis), Rpl6 (tissue regeneration), Fabp4 (fatty acid metabolism), and Proc (blood coagulation). Males were more sensitive to many renal end points suggestive of toxicity. At the end of exposure, toxicity was noted at all dose levels, and the 75 µg/kg group exhibited significant effects in liver and kidney/body weight ratios, reduced BUN, increased serum monocytes, and multiple signs of histopathology indicating that a no-observed-adverse-effect level could not be determined for any dose level.

Effect of fasting and fasting-refeeding on the structure, metabolism and transport functions of renal cortical proximal tubules from different kidney regions

Effect of fasting and fasting-refeeding on the structure, metabolism and transport functions of renal cortical proximal tubules from different kidney regions

Transcriptional Suppression of Renal Antioxidant Enzyme Systems in Guinea Pigs Exposed to Polymerized Cell-Free Hemoglobin.

Hemoglobin-based oxygen carriers (HBOCs) are being developed as oxygen and plasma volume-expanding therapeutics though their potential to promote oxidative tissue injury has raised safety concerns. Using a guinea pig exchange transfusion model, we examined the effects of polymerized bovine hemoglobin (HbG) on the transcriptional regulation, activity, and expression of the renal antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). HbG infusion downregulated the mRNA levels for genes encoding SOD isoforms 1-3, GPx1, GPx3, GPx4, and CAT. This transcriptional suppression correlated with decreased enzymatic activities for SOD, CAT, and GPx. Immunostaining revealed decreased protein expression of SOD1, CAT, and GPx1 primarily in renal cortical tubules. DNA methylation analyses identified CpG hypermethylation in the gene promoters for SOD1-3, GPx1, GPx3, and GPx4, suggesting an epigenetic-based mechanism underlying the observed gene repression. HbG also induced oxidative stress as evidenced by increased renal lipid peroxidation end-products and 4-HNE immunostaining, which could be the result of the depleted antioxidant defenses and/or serve as a trigger for increased DNA methylation. Together, these findings provide evidence that the renal exposure to HbG suppresses the function of major antioxidant defense systems which may have relevant implications for understanding the safety of hemoglobin-based products.

Comparison between the ameliorative potentials of canagliflozin and metformin on the testicular damage in diabetic rats

To evaluate the Renoprotective efficacy of melatonin against long term exposure induced changes of dimethylbenz(a)anthracene (DMBA), cell proliferation and DNA synthesis was determined in the epithelial cells of cortical and medullary renal tubules in female and male mice applying quantitative autoradiographic analysis and using 3H thymidine as a radioactive label. A total of 30 male and female adult albino mice were divided into 3 groups, each of 10 individuals: control (group C), DMBA exposed (group D) and DMBA/melatonin exposed (group D+M) mice. In female mice, long term exposure for 150 days to a single injection of DMBA (10mg/ 100g b.w.) stimulated the incorporation rate of 3H thymidine into the epithelium of cortical renal tubules by 6774% compared to control. The number of grains over labeled nuclei was reduced by 57.1%. Daily injected with melatonin (100 g/ 100g b.w.) during the last 60 days of exposure to a single dose of DMBA attenuated cell division rate of the epithelial cells by 80% compared to group D, but remained 1275% higher than that of group C. The mean grain count over labeled nuclei was increased by 59.5% compared to group D, but remained 31.5% lower than that of control. In the medullary portion of the renal tubules, DMBA induced changes were less pronounced than that in the cortical area. The cell division was stimulated by 833% compared to control and remained 8.1x lower than the percentage increase in the cortical part. The mean grain count over labeled nuclei was reduced by 40.4% compared to group C. Daily injected with melatonin (100 g/ 100g b.w.) during the last 60 days of exposure to a single dose of DMBA reduced the mitotic cell division by 83.9% compared to group D and thereby showing a similar effect as in the cortical part of the renal tubules. Compared to group C, the 3H labeling index remained 50% higher. In the cortical portion, the comparable value was 1275% higher than that of control. The mean grain count over labeled nuclei was increased by 26.2% compared to group D and remained 24.8% lower than in group C.

Histological study of the renal cortical proximal and distal tubules in adult male albino rats following prolonged administration of titanium dioxide nanoparticles and the possible protective role of l-carnosine

Introduction Titanium dioxide (TiO2) nanoparticles (NPs) are among the most widely used NPs in different industries and in a variety of health products, thus increasing the potential risk of environmental exposure to TiO2 in the kidney. Aim The aim of this study was to investigate histological changes in renal cortical proximal and distal tubules following prolonged administration of TiO2 NPs and the possible protective role of l-carnosine. Materials and methods Thirty-five adult male albino rats were distributed randomly among three groups as follows: group I (A, B, and C) (control groups), group II (TiO2 NPs group), and group III (TiO2 NPs and l-carnosine). Animals of groups II and III received TiO2 NPs at a dose of 150 mg/kg body weight and TiO2 NPs at a dose of 150 mg/kg along with l-carnosine at a dose of 10 mg/kg/day intraperitoneally, respectively, daily for 30 days. At the end of the experiment, all animals were killed under ether anesthesia. Kidneys were dissected and specimens were processed for histological examination using a light microscope after H&E and periodic acid Schiff stains. Other specimens were processed for electron microscopic examination. TiO2 NPs were characterized by a transmission electron microscope, a Nano Zetasizer particle analyzer, and X-ray diffraction. Results In the control groups, both proximal and distal tubules showed a classical histological structure. In group II, renal tubular cells showed evident changes in the form of cytoplasmic vacuolation, cell lysis, and extrusion of cells into the tubular lumen. Most of the nuclei appeared dark and shrunken. In group III, there was marked histological improvement. Conclusion Prolonged systemic exposure to TiO2 NPs induced degenerative changes in renal cortical tubules that were evident histologically. Also, it was found that l-carnosine could potentially be a protective agent that can ameliorate the hazardous effect of TiO2 NPs on the kidney.