Kidney Of Female Rats Research Articles

Histopathological Studies on the Effect of Taurine Against Etoposide-Induced Acute Liver and Kidney Toxicity in Female Albino Rats

Etoposide (ETP) is a topoisomerase Ⅱ (TOP Ⅱ) inhibitor and one of the leading chemotherapeutic drugs for treating a wide variety of tumors. However, ETP induced hepatotoxicity and nephrotoxicity limits its clinical use. This study aims to investigate the protective potential of taurine (Tau) to mitigated histopathological changes in the liver and kidneys of female albino rats treated with ETP. A total of 18 female rats were divided into three groups; control group, ETP-exposed group received intraperitoneal injection of ETP on the first 3 days of the study for a total cumulative dose of 44 mg/kg to induce hepatotoxicity and nephrotoxicity, ETP + Tau group received ETP as stated previously with 400 mg/kg/day of Tau via oral gavage for 15 days. Sections from the liver and kidney were evaluated under light microscope and ETP-exposed group revealed vascular congestion, chronic inflammatory cell infiltration predominantly lymphocytes, edema, vacuolar degeneration, atypical cells, pyknosis, and necrosis while liver and kidney sections of rats treated with combination of ETP + Tau group exhibited marked alleviation of the histopathological damage. The study concludes that treatment with ETP induced marked structural damages in the liver and kidney and such morphological damages are effectively diminished by administering Tau.

Novel Evidence for an Enhanced Intrarenal Machinery of Estrogen Biosynthesis in the Female Rat Kidney

Novel Evidence for an Enhanced Intrarenal Machinery of Estrogen Biosynthesis in the Female Rat Kidney

Evaluation of the Subacute Toxic Effects of the Alkaloids of the Seeds of Peganum harmala L in the Liver, Kidney and Ovary of Female Rats

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Toxicological Outcome of Combined Exposure to Potassium Dichromate and Levonorgestrel in the Kidney of Female Rats

Co-exposure to chromate (VI) compound and oral contraceptives is common in our environment especially among women working in chromate-related industries. Exposure to either chromate (VI) or oral contraceptives is linked with the etiology of several diseases including cancers and renal injury. However, there is paucity of information on the toxic effect of combined co-exposure to both compounds. The present study examines the toxicity of combined exposure to potassium dichromate (PDC) and an oral contraceptive, levonorgestrel in the kidney of female rats. Control animals were fed distilled water, while experimental rats were injected 12 mg/kg body weight of PDC once a week for six weeks and oral daily exposure to 15µg/kg body weight of levonorgestrel either alone or in combination. Absolute and relative kidney weight, renal function, oxidative stress and pathological lesion were assessed in plasma and kidney of control and experimental rats. The PDC and levonorgestrel significantly (p<0.05) increased plasma urea creatinine and malondialdehyde levels in treated-rats, while renal superoxide dismutase and glutathione-S-transferase activities were reduced by both compounds. Moreover, histopathological lesions including necrotizing nephritis was observed in the kidney of PDC-treated rats, while tubular epithelial degeneration and necrosis was observed in levonorgestrel-treated rats. Combined exposure to both compounds aggravated the increase in urea, creatinine and renal damage. Additionally, the antioxidant enzymes were further repressed in the co-treatment group. The study suggests that combined exposure to potassium dichromate and levonorgestrel worsened nephrotoxicity in rats by increasing oxidative stress.

Sex and species differences in epithelial transport in rat and mouse kidneys: Modeling and analysis.

The goal of this study was to investigate the functional implications of sex and species differences in the pattern of transporters along nephrons in the rat and mouse kidney, as reported by Veiras et al. (J Am Soc Nephrol 28: 3504–3517, 2017). To do so, we developed the first sex-specific computational models of epithelial water and solute transport along the nephrons from male and female mouse kidneys, and conducted simulations along with our published rat models. These models account for the sex differences in the abundance of apical and basolateral transporters, glomerular filtration rate, and tubular dimensions. Model simulations predict that 73% and 57% of filtered Na+ is reabsorbed by the proximal tubules of male and female rat kidneys, respectively. Due to their smaller transport area and lower NHE3 activity, the proximal tubules in the mouse kidney reabsorb a significantly smaller fraction of the filtered Na+, at 53% in male and only 34% in female. The lower proximal fractional Na+ reabsorption in female kidneys of both rat and mouse is due primarily to their smaller transport area, lower Na+/H+ exchanger activity, and lower claudin-2 abundance, culminating in significantly larger fractional delivery of water and Na+ to the downstream nephron segments in female kidneys. Conversely, the female distal nephron exhibits a higher abundance of key Na+ transporters, including Na+-Cl− cotransporters in both species, epithelial Na+ channels for the female rat, and Na+-K+-Cl−cotransporters for the female mouse. The higher abundance of transporters accounts for the enhanced water and Na+ transport along the female rat and mouse distal nephrons, relative to the respective male, resulting in similar urine excretion between the sexes. Model simulations indicate that the sex and species differences in renal transporter patterns may partially explain the experimental observation that, in response to a saline load, the diuretic and natriuretic responses were more rapid in female rats than males, but no significant sex difference was found in mice. These computational models can serve as a valuable tool for analyzing findings from experimental studies conducted in rats and mice, especially those involving genetic modifications.

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.

Histological study for the effect of sesame oil on liver and kidney in female albino rats

The current study was conducted to find out the effect of sesame oil on white female rats by studying changes in the histological structure of the liver and kidneys. The study included 20 animals divided into 4 groups; each group included 5 animals dosed with different doses volume (0.5'0.8' 1 ml)/kg. The period of dosing was for a month between one day and another. At the end of the experiment, the animals were sacrificed and the tissue of the liver and kidney was taken and preserved with (10% formalin) for histological procedure, Histologically results showed that sesame oil had a safety effect on both tissues, and the result was very similar to the normal tissue.

Sexual dimorphisms in renal mitochondrial bioenergetics

BackgroundStudies have shown that men have higher incidences of end‐stage renal disease than women at every point across the lifespan. Animal models for various renal diseases have similar occurrence with males being affected more frequently. Recent efforts have been heavily focused on delineating the mechanisms behind these sex‐based differences from various angles, with the mitochondria being highlighted as a target for sex difference‐related renal pathologies. The goal of this study is to investigate the sexual dimorphisms of renal mitochondria and their dependency on renal hemodynamics before disease onset.MethodsMitochondria were isolated from PBS‐flushed kidneys of Sprague Dawley male (SDM) and female (SDF) rats at 11 weeks of age using differential centrifugation. Renal cortex (SDMC vs SDFC) and medulla (SDMMvs SDFM) were separated for individual measurements. Mitochondrial membrane potential and hydrogen peroxide production were measured in spectrofluorimetry using the fluorescent dyes TMRM and Amplex Red, respectively. A portion of mitochondria were submitted to a histology core for electron microscopy. Additionally, mitochondrial oxygen consumption rate (OCR) was also assessed using Seahorse assay. Lipid peroxide radical formation was detected using electron paramagnetic resonance (EPR) with in vivo spin trapping. As a measure of renal function, GFR was assessed using FITC‐Inulin in conscious animals.ResultsElectron microscopy revealed similar yield of mainly round‐shaped isolated mitochondria with retained cristae and membrane structures in all groups. SDFM showed a higher membrane potential than SDMM (238.1±12.4 vs 162.0±8.8 au, p<0.001; respectively). Both SDFC and SDFM had higher hydrogen peroxide production in comparison to their male counterparts (cortex: 99443.7±3061.7 vs 69943.4±1708.6 au/protein, p<0.001; respectively. medulla: 113366.7±5430.7 vs 60613±2297.1 au/protein, p<0.001; respectively). Overall female mitochondria exhibited decreases in their basal, ATP‐linked, leaked OCRs as well as spare capacity compared to males (spare capacity: cortex: 5.9±0.6 vs 14.3±1.3, p<0.001; respectively. medulla: 4.9±0.6 vs 11.6±0.7 pmol/min/protein, p<0.001; respectively). EPR showed similar lipid peroxide radical levels in both sexes and sections of kidney. In the next part of the study, we explored if renal mitochondrial bioenergetics correlated with the GFR of the animal. Our data show the following GFR values for male and female rats as normalized to two kidney weights (2KW) and 2KW/ total body weight (2KW/TBW), respectively: 1.4±0.2 vs 0.8±0.1 mL/min/2KW, p=0.1416 and 0.5±0.1 vs 0.2±0.02 mL/min/2KW/TBW, p=0.0143. We did not observe any correlation between mitochondrial membrane potential and ROS production (measured in the isolated renal cortical mitochondria) with GFR in male or female rats (n= 5 in each group).ConclusionsOverall, we show here that female renal mitochondria exhibit lower oxygen consumption, higher ROS emission, and membrane potential vs males; however, lipid peroxidation is similar. Currently, we do not see a correlation between mitochondrial bioenergetics and GFR. More studies designed with higher statistical power are required to further elucidate the relationship between renal blood flow and mitochondrial bioenergetics.

FABP1: A Potential Biomarker for Nephropathy in Type II Diabetes

Aims of the studyNephropathy is an important and frequent complication of diabetes mellitus. Diabetic nephropathy (DN) is also the leading cause of end stage renal disease in most parts of the world. Albuminuria is the hallmark of DN although recent observations suggest that non‐albuminuric nephropathy accounts for as much as 40% of all cases of DN. There is a need for additional and more accurate biomarkers for diagnosis and prognosis of DN. Fatty acid binding protein 1 (FABP1) is normally expressed in the liver but also in the kidney in human and animal DN models. However, it has not been detected in normal rat kidneys. We hypothesized that FABP1 is consistently elevated in the kidneys of experimental nephropathy of type II diabetes and could be a diagnostic biomarker and may have a potential pathogenic role.MethodsMale and female ZSF1 rats were used as an experimental model for nephropathy in type II diabetes and CD rats (non‐diabetic rats) were used as controls. Animals were studied from 8th week and sacrificed at 40 weeks. Kidneys were harvested and tissue homogenates were used for total RNA extraction for Next Gen sequencing and protein extraction for western blots. Serum and urine samples were also collected at the start and end of the study to quantitate the renal function and excretion of markers.ResultsThe ZSF1 rats spontaneously developed obesity, diabetes and hyperlipidemia as expected. Male rats developed more severe hyperglycemia, renal failure and proteinuria (data previously communicated) than females. Next Gen Sequencing of kidney tissue revealed amongst other findings a 1396‐fold increased expression of FABP1. Examination of kidney tissue protein homogenates for the expression of FABP1 showed increased expression especially in the male ZSF1 rats. Examination of urine samples for the presence of FABP1 by ELISA showed remarkably increased levels (12 to15‐fold in males and 6 to 7‐fold in females) increase compared to CD rats. (See figure 1)ConclusionsBoth male and female ZSF1 rats developed metabolic syndrome and nephropathy although the disease was much more severe in male rats. FABP1 was expressed more in male rat kidneys compared to female and control rat kidneys. Additionally, the urine excretion of FABP1 was increased in both male and female ZSF1 rats compared to control rats. These data suggest FABP1 may be a potential biomarker in DN. Additional studies are warranted to examine the mechanisms driving the robust renal FABP1 production/excretion and the possible pathogenic role and potential of FABP1 as a therapeutic target in DN.

Ameliorative Effect of Mushroom Extracts against Butyl Paraben Induced Toxicity in Liver and Kidney in Female Albino Rats.

Ameliorative Effect of Mushroom Extracts against Butyl Paraben Induced Toxicity in Liver and Kidney in Female Albino Rats.

Hepato- and Nephro-Effect of Sphenostylis stenocarpa– Formulated Diet on Dexamethasone-Treated Pregnant Rats

This study sought to investigate the effect of Sphenostylis stenocarpa-formulated diet on hepatic and renal parameters of dexamethasone-treated pregnant rats. Sphenostylis stenocarpa were locally sourced from a market in Ado Ekiti. They were milled into powder and used in formulating feed for experimental animals. Fifteen female pregnant rats were divided in three groups of five each. Animals in group A were exposed to standard animal feed only. This served as the control group. Those in group B were exposed to Sphenostylis stenocarpa-formulated diet + 0.3 mg/kg body weight of dexamethasone, while those in group C were exposed to Sphenostylis stenocarpa-formulated diet. At the end of the eight days treatment, animals were sacrificed and blood sample, liver and kidney were collected. Exposure of pregnant rats to dexamethasone was observed to significantly (p<0.05) increased the activities of plasma aspartate amino transaminase (AST) and alanine amino transferase (ALT) as well as the concentrations of plasma total protein, bilirubin, creatinine and urea when compared with those in animals in the control as well as those fed with S. stenocarpa-formulated diet only. The results further showed that pregnant rats fed with S. stenocarpa-formulated diet only had no significant difference on plasma hepatic and renal biomarkers when compared with those in the control group. The results of liver and kidney homogenates are similar to those observed in the plasma. Exposure of animals to dexamethasone adversely unhinged hepatic and renal biomarkers investigated in the study. The study also revealed that P. biglobosa seed is beneficial to the health of the liver and kidney of pregnant female rats.

Impact of tartrazine and curcumin on mineral status, and thyroid and reproductive hormones disruption in vivo

Endocrine disrupters (EDCs) are naturally occurring or man-made substances that either mimic or obstruct the functions of oestrogens and androgens, thyroid hormones, as well as microminerals in the body. The present work aimed to evaluate the effects of oral administration of tartrazine and curcumin, synthetic and natural dyes, respectively, on thyroid hormones (T3, T4, and TSH), female reproductive hormones (oestrogen, progesterone, LH, and FSH), and minerals (iron, copper, zinc, sodium, potassium, and chloride) in plasma, liver, and kidney of female rats after 15, 30, and 45 d of treatment. The rats were treated with admissible daily intake (ADI) and 10× ADI (9.6 and 96 mg/kg/body weight for tartrazine, 3.85 and 38.5 mg/kg/body weight for curcumin, respectively). Results showed significant changes in thyroid and female reproductive hormones, especially, in the tartrazine-treated groups as compared to the control. Low and high doses of tartrazine and curcumin significantly (p < 0.05) decreased iron, copper, and zinc concentrations in plasma, whereas, the concentrations of sodium and copper in liver and kidney increased. Both tartrazine and curcumin, at ADI and 10× ADI, resulted in lower LH levels after 30 and 45 d of treatment. After 30 d, low and high dose of tartrazine significantly decreased T4, oestrogen, and FSH levels; whereas, progesterone level increased. The results demonstrated that hormone secretion and mineral content in tissues are severely affected at ADI and higher concentrations of tartrazine and curcumin. These observations suggested that lower doses of these dyes might be a safer option for their usage in foods and pharmaceuticals.

The subacute toxicity effects of aged Tualang (Koompassia excelsa) honey with high 5-hydroxymethylfurfural content in rats

Tualang honey (TH) stored for more than 12 months is characterised as aged TH (ATH). Surprisingly, majority of the general public is unaware of the recommended consumption period for honey, since most honeys marketed locally have no determined expiry dates. The present work determined 5-hydroxymethylfurfural (HMF) content in four-year stored ATH, and evaluated the effects of ATH upon repeated dose during 28-day oral toxicity study. The HMF concentration in ATH was determined using HPLC. Animal toxicity study was conducted by treating Sprague Dawley rats with distilled water (control), 200, 1,000, 2,000 mg/kg/day ATH, or 2,000 mg/kg/day fresh TH for 28 days. The HMF concentrations were significantly high, exceeding the international maximum limit set for tropical honey (> 80 mg/kg). ATH did not affect the general conditions and behaviour of the rats. Nevertheless, female rats exhibited significant increase in creatinine and oestradiol levels when treated with 1,000 mg/kg/day ATH. The left kidney’s weight of those treated with 200 mg/kg/day ATH also significantly decreased. Further, histological findings revealed that there were reductions in the Bowman’s space and poorly defined glomerular boundary in female rats treated with 1,000 mg/kg ATH. In contrast, all parameters in male rats were statistically unaffected by ATH. The present work suggested that ATH with remarkably higher HMF concentrations modified the kidneys of female rats but not those of the male rats, which indicated sex-based variation. The no-observed-adverse-effect level was 2,000 mg/kg/day for male rats, and less than 200 mg/kg/day for female rats.

Hepatotoxic and Nephrotoxic Potential of an Anticancer Drug Paclitaxel after Prolong Exposure in Adult Female Rats

Paclitaxel (PTX) is a microtubule inhibitor commonly used as a potent chemotherapeutic agent for treatment of a variety of cancers including breast cancer. PTX is causing several serious side effects during and after chemotherapy related to metabolic and renal dysfunctions. Clinical and non-clinical studies on PTX exposure and histopathological changes in liver and kidney are limited; therefore present study was designed to evaluate hepatotoxicity and nephrotoxicity of PTX in adult female rats. In this regimen, equivalent therapeutic doses of PTX (1.6 and 3.2 mg/kg BW) were intravenously administered weekly for six weeks. After six weeks of exposure, liver and kidney of PTX exposed and control rats were extirpated, fixed in 10% neutral buffered formalin for paraffin sectioning. As per protocol, sections of liver and kidney were cut at 8 µm and finally stained with Haematoxylin and Eosin. Our results demonstrated that intermittent exposure to PTX for six weeks (once per week) induced substantive histopathological changes in liver (hepatocyte derangement, blood clotting, and CV dilatation) and kidney (glomerular atrophy, vascular congestion, dilation of distal tubules) of female rats.

Assessment of Parkia biglobosa on Hepatic and Renal Biomarkers of Dexamethasone-Exposed Pregnant Rats

Aim: This study sought to investigate its effect on hepatic and renal biomarkers of female pregnant rats.
 Place and Duration: This work was carried out in the Department of Medical Biochemistry and Department of Science Laboratory Technology, Ekiti State University, Ado Ekiti between January and June 2021.
 Methodology: Locust bean seeds were purchased from an open market in Ado Ekiti, Nigeria and were processed using standard method. Fifteen female pregnant rats were divided into three groups of five each. Animals in group A were exposed to standard animal feed only. This served as the control group. Those in group B were exposed to animal feed mixed with locust beans + 0.3 mg/kg body weight of dexamethasone, while those in group C were exposed to animal feed mixed with locust beans only. At the end of the eight days treatment, animals were sacrificed and blood sample, liver and kidney were collected.
 Results: Exposure of pregnant rats to dexamethasone was observed to significantly (p<0.05) increased the activities of plasma aspartate amino transaminase (AST) and alanine amino transferase (ALT) as well as the concentrations of plasma total protein, bilirubin, creatinine and urea when compared with those in animals in the control as well as those treated with P. biglobosa only. The results further showed that administration of P. biglobosa only had no significant effect on plasma hepatic and renal biomarkers except urea which was significantly lower than those in the control group as well as those treated with dexamethasone. The results obtained from liver and kidney homogenate respectively are similar to those observed in the plasma.
 Conclusion: Exposure of animals to dexamethasone adversely unhinged hepatic and renal biomarkers investigated in the study. The study also revealed that P. biglobosa seed is beneficial to the health of the liver and kidney of pregnant female rats.

Limosilactobacillus fermentum Strains with Claimed Probiotic Properties Exert Anti-oxidant and Anti-inflammatory Properties and Prevent Cardiometabolic Disorder in Female Rats Fed a High-Fat Diet.

This study assessed the effects of a mixed formulation containing Limosilactobacillus (L.) fermentum 139, L. fermentum 263, and L. fermentum 296 on cardiometabolic parameters, inflammatory markers, short-chain fatty acid (SCFA) fecal contents, and oxidative stress in colon, liver, heart, and kidney tissues of female rats fed a high-fat diet (HFD). Female Wistar rats were allocated into control diet (CTL, n = 6), HFD (n = 6), and HFD receiving L. fermentum formulation (HFD-LF, n = 6). L. fermentum formulation (1 × 109CFU/mL of each strain) was administered two twice a day for 4weeks. Administration of L. fermentum increased acetate and succinate fecal contents and reduced hyperlipidemia and hyperglycemia in rats fed a HFD (p < 0.05). Administration of L. fermentum decreased low-grade inflammation and improved antioxidant capacity along the gut, liver, heart, and kidney tissues in female rats fed a HFD (p < 0.05). Administration of L. fermentum prevented dyslipidemia, inflammation, and oxidative stress in colon, liver, heart, and kidney in female rats fed a HFD.

Effects of Smokeless Tobacco on the Histology and Functioning of Proximal Convoluted Tubules of the Kidneys of Female Albino Rats

Aims: The consumption of oral form of smokeless tobacco has increased rapidly. Its use is associated with increased risk of chronic diseases like diabetes, myocardial infarction, liver disorders, cerebrovascular accidents and many other health issues. Use of tobacco in any form either smoked or chewed form leads to the absorption of nicotine which spontaneously moves into the bloodstream where it is circulated throughout the body system. Hence through this study an effort is being made to evaluate the effects produced by the locally available brand of smokeless tobacco on the histology and functioning of proximal convoluted tubules of the kidneys of the female Swiss albino rats.&#x0D; Place and Duration of Study: The study was conducted in Sindh Agricultural University, Tandojam and further lab work was carried out in Isra University Hyderabad.&#x0D; Methodology: 30 adult female Swiss albino rats were randomly selected. They were divided into three groups (n=10). Group A were taken as control. Group B&amp;C comprised of rats which were given 5 %&amp; 10% of smokeless tobacco respectively along with their chow diet. The feed and water were given ad libitum. Animals were sacrificed on 31st day and their kidneys were removed and weighed. The specimens were processed routinely for examination under light microscope. The sections were stained using H &amp; E stains and examined under light microscope. Blood samples for analysis of creatinine and urea were collected.&#x0D; Results: A significant decrease in the weight of the kidneys, an increase in the levels of creatinine and urea were observed (P value = 0.001). Kidneys of both B &amp; C groups showed edema, congestion and presence of cast cells when compared with the kidneys of the control group.&#x0D; Conclusion: From these observations, it can be inferred that the exposure of female Swiss albino rats to the smokeless form of Tobacco is associated with structural and functional damage of the kidneys.

Pharmacokinetics and Tissue Distribution of Combined Triptolide and Paeoniflorin Regimen for Percutaneous Administration in Rats Assessed by Liquid Chromatography-Tandem Mass Spectrometry.

Triptolide (TP) has shown potential in rheumatoid arthritis (RA) treatment, but the narrow therapeutic window limits its clinical application. In clinical practice, the compatibility of Tripterygium wilfordii and Paeonia lactiflora is often used to attenuate the toxicity of TP, but its compatibility mechanism has not been fully elucidated. The aim of this study was to investigate the pharmacokinetics and tissue distribution of a combined regimen of TP and paeoniflorin (PF) after transdermal administration in male and female Sprague Dawley (SD) rats via a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The results showed that after percutaneous administration of TP and PF, there was no significant difference in AUC (0-t) (area under the curve) of TP, the peak concentration decreased by 58.17%, and the peak time was delayed. The AUC (0-t) of PF increased significantly (P < 0.01), the peak-reaching concentration and AUC (0-∞) increased, and the half-life and average retention time were shortened, indicating that TP absorption in rats may be delayed. After percutaneous administration of TP and PF, the content of TP in the heart, liver, spleen, lungs, and kidneys of male rats significantly decreased at 2 h (P < 0.05) and the drug concentration in the liver tissues significantly decreased at 2 h, 4 h, and 8 h (P < 0.05). The TP content in the spleen of female rats significantly decreased at 2 h and 4 h (P < 0.05) and also decreased in other tissues, but not significantly. After percutaneous administration of TP and PF, the PF content in the heart, liver, spleen, lungs, and kidneys of male and female rats had no significant difference. However, after percutaneous administration of TP and PF, the TP concentration in the skin increased, suggesting that the amount of TP retained in the skin increased, thereby reducing its content in blood and tissues, producing a reduction in toxicity effect.

VDR, CYP2R1 and CYP27B1 Genes Are Differentially Expressed in Male`s and Females Tissues of Wistar Rats

Effect of vitamin D on gene expression has been widely investigated in vitro; however, in vivo action of vitamin D supplementation has been much less analysed in this context. Moreover, recent findings suggest that the effect of vitamin D supplementation may be sex-specific. The aim of our study was to investigate how vitamin D supplementation affects the expression of vdr, cyp2r1 and cyp27b1 genes in the liver, fat, brain and kidney of male and female rats. 36 adult Wistars rats (18 male and 18 females) were divided into 3 groups obtaining the same standard diet, differing only in the dose of vitamin D (group I - no supplementation, group II 1000 IU/kg of vitamin D, group III 5000 IU/kg of vitamin D). After 3 months of the experiment, animals were euthanised, and samples of tissues were collected from all animals. RNA was isolated using the Purelink RNA isolation kit (Thermofisher). RNA was reverse transcribed using High-Capacity cDNA Reverse Transcription Kit (Thermofisher). qPCR was performed using TaqMan™ assays and TaqMan™ Fast Advanced Master Mix on Quant Studio 7 instrument (Thermofisher). Data were analysed using SAS software. In the liver, we observed that the expression of the vdr gene was ~5 fold higher and cyp2r1 was ~2 fold higher in females compared to males (p<0.0003) (p<0.0002) respectively. In adipose tissue expression of cyp27b1 was ~1.8 fold higher (p<0.014) in females compared to males. In the kidney expression of vdr and cyp2r1 was slightly higher in females (fold change- (fc) 1.18 p<0.03) (fc=1.37, p<0.0001), while expression of cyp27b1 was 1.7 fold higher in males (p<0.013). In the brain, we observed slightly increased expression of cyp2r1 and cyp27b1 genes in females when compared to males (fc=1.14 p<0.0001), fc=1.23 p<0.01). Supplementation with 5000 IU/kg of vitamin D resulted in the decrease in the expression of vdr, cyp2r1 and cyp27b1 in the kidney when both sexes were analysed together(p<0.0127, p<0.0326, p<0.0326) but this decline was only statistically significant for vdr in males when sexes were analysed separately (p<0,0403). In the liver of males expression of vdr gene tended to increase and expression of cyp27b1 tended to decrease after vitamin D supplementation (p<0.06) (p<0.0501). In the adipose of males expression of cyp27b1 was downregulated by the high dose of vitamin D (p<0.04) but not in females. In the brain of males, we observed a slight decrease in the expression of cyp2r1 in a group obtaining 5000 IU/kg of vitamin D when compared to animals obtaining 1000 IU/kg (p<0.025). Concluding, our study shows that in a number of tissues of Wistar rats, expression of vdr, cyp27b1, and cyp2r1 is higher in females when compared to males. The only exception is the expression of cyp27b1 in the kidney, where it is higher in males. Moreover, the effect of vitamin D supplementation on the expression of these genes is weak and more evident in males and when high doses (5000 IU/kg) of vitamin D was used.

Thyroid Pathological Consequences Induced by Caffeine in Female Rats

Objective: this study was designed to investigate the histopathological changes induced by caffeine onthyroid, liver and kidneys in female rats. Caffeine is a central nervous stimulant of methyl xanthine class ofdrugs, it has many hormonal and metabolic effects.Method: twenty-four adult female rats was split in to four equal categories of 6 rats in each group as thefollowing: Group1,control group received distilled water only by oral gavage. Group2, received 35mg\kg ofcaffeine solution. Group3, received 75mg\kg of caffeine and Group4, received 150mg\kg of caffeine. Theexperiment continued for 40 days. After 24 hours of the end of experiment, the animals were sacrificed andblood has been withdrawn from vena cava to prepare serum for hormonal analysis, whereas liver, kidneysand thyroid were excised and fixed in formalin solution for histopathological processing.Results: caffeine ingestion cause significant reduction in thyroid function (reduction in T3, T4 and TSH)in all treated groups compared to control group in addition histopathological study show enlargement ofthyroid follicle with thinning of lining epithelium of acini, vacuolation of both renal tubules, hepatocytesand vascular congestion of these organs.Conclusion: Caffeine consumption in high doses causes many histologic and hormonal effects in the studiedorgans.