Normal Diet Rats Research Articles

Effects of Composite Probiotic Food on Urinary, Serum Biochemical and Oxidative Stress Parameters in a Urolithiatic Rat Model.

Prevention, management or cure of diseases through dietary approaches is becoming increasingly important. Research suggests that probiotic, oxalate-degrading Lactobacillus species administered via a milk and cereal food can prevent kidney stones while also addressing nutritional deficiencies and maintaining essential calcium levels. This study investigates the effect of a composite probiotic milk beverage on urolithiatic rats. Probiotic milk-barley beverage (PMBB) was prepared by fermentation of milk enriched with barley (Hordeum vulgare) flour using starter culture containing oxalate-degrading probiotic strains (Lacticaseibacillus rhamnosus strains MTCC5945 and MTCC25062, Lactobacillus helveticus MTCC5463 and Lactiplantibacillus plantarum M11). Cumin and common salt were used as flavourings. Unfermented milk-barley base (C) served as control. Wistar rats were divided in four groups (N=6). Normal control (NC) group received normal rat diet, and to induce kidney stones, ethylene glycol (0.75 %) and ammonium chloride (1 %) were administered to the disease control (DC) group, PMBB and control (C) groups for 28 days. PMBB and C groups received 1 mL of probiotic milk and barley beverage and unfermented milk-barley base from day 15 to day 28. Indicators of urolithiasis were studied. PMBB significantly (p<0.05) increased urine output, decreased urine oxalate concentrations and increased creatinine, calcium and uric acid concentrations. Serum parameters such as concentrations of calcium, uric acid, urea and creatinine increased significantly (p<0.05) in DC rats, but decreased significantly (p<0.05) in the PMBB group. In addition, serum concentrations of magnesium and osteopontin decreased more significantly in DC rats than in the PMBB ones. The increase in malondialdehyde and decrease in reduced glutathione concentrations observed in the DC group were significantly lower in the PMBB group. The histomorphology of the kidney tissue of DC rats showed calcium oxalate crystal aggregates in the tubules, indicators of renal injury, tubular dilatation, enlarged urinary space and shrunken glomeruli. The PMBB group showed an improvement in the renal histological architecture. Analysis of the caecal digesta of the rats showed a significantly (p<0.05) higher mass fraction of fatty acids (acetic and propionic) in the treatment group. The results show the potential of PMBB in the dietary control of urolithiasis. This study focuses on the antiurolithiatic prospect of a composite probiotic milk beverage produced with oxalate-degrading culture. It also points to a new functional food form that shows promising health benefits in nutrition of patients with urolithiasis.

The Effects of Caloric Restriction on Inflammatory Targets in the Prostates of Aged Rats.

Numerous animal models have demonstrated that caloric restriction (CR) is an excellent tool to delay aging and increase the quality of life, likely because it counteracts age-induced oxidative stress and inflammation. The aging process can affect the prostate in three ways: the onset of benign prostatic hyperplasia, prostatitis, and prostate cancer. In this study, we used 14 aged male Sprague Dawley rats, which were allocated into two groups, at the age of 18 months old. One group was fed ad libitum (a normal diet (ND)), and the other group followed a caloric restriction diet with a 60% decrease in intake. The rats were sacrificed at the age of 24 months. By immunohistochemical (IHC) and Western blot (WB) analyses, we studied the variations between the two groups in immune inflammation and fibrosis-related markers in aged prostate tissues. Morphological examinations showed lower levels of prostatic hyperplasia and fibrosis in the CR rats vs. the ND rats. The IHC results revealed that the prostates of the CR rats exhibited a lower immune proinflammatory infiltrate level and a reduced expression of the NLRP3 inflammasome pathway, together with significantly reduced expressions of mesenchymal markers and the profibrotic factor TGFβ1. Finally, by WB analysis, we observed a reduced expression of ERα, which is notoriously implicated in prostate stromal proliferation, and increased expressions of SOD1 and Hsp70, both exerting protective effects against oxidative stress. Overall, these data suggest that CR brings potential benefits to prostatic tissues as it reduces the physiological immune-inflammatory processes and the tissue remodeling caused by aging.

Prepuberty is a window period for curcumin to prevent obesity in postnatal overfed rats.

Overnutrition in early life increases the risk of obesity and metabolic diseases. We investigated the effects and the window period of a curcumin (CUR) diet on postnatal overfed rats. Male rats aged 3 days were randomly divided into normal litters (NL, 10 pups/litter) and small litters (SL, 3 pups/litter). After weaning (Week 3, W3), NL rats were fed a normal diet (NL) and SL rats were fed a normal diet (SL) or 2% CUR diet from weaning (W3) (SL-CURW13), beginning of puberty (W6) (SL-CURW16), or end of puberty (W8) (SL-CURW18) for 10 weeks. Body weight, glucose intolerance and hyperlipidemia in the SL rats were higher than in the NL rats, especially after puberty. After the CUR intervention, SL-CURW13 and SL-CURW16 rats showed lower body weight gain, adipose tissue weight and mRNA level of C/EBPα in SAT, along with higher mRNA levels of β-catenin. There was no difference between SL and SL-CURW18 rats. Glucose tolerance, serum lipids and hepatic lipids recovered to normal in the SL-CURW13 rats, but only partially in the SL-CURW16 and SL-CURW18 rats. Prepuberty is a window period for CUR intervention to improve programmed outcomes in postnatal overfed rats. Overnutrition during the first 1000 days of life has persistent negative effects on metabolism. Strategies should be taken to prevent overnutrition in early life to reduce the risk of obesity and metabolic disease in later life. A small-litter rat model was utilized to simulate early-life overnutrition in humans. We investigated the different effects and critical period for curcumin intervention on postnatal overfed rats. Dietary curcumin intervention before puberty could effectively transform nutritional programming to reduce obesity and metabolic disorders caused by early-life overnutrition, and an earlier intervention might predict a better outcome.

The Effects of Gluten on Weight Gain, Hematological, Biochemical, and Various Endocrinological Parameters.

This study is aimed to compare the effects of nutrition which has been enriched with different amounts of gluten to gluten-free diets on weight gain, diabetogenic state, hematological, and biochemical parameters. A total of 40 newly weaned male Wistar albino rats used in the study were randomized into 4 different groups based on the gluten rations they were given. Following 12 weeks of diet they were killed and intracardiac blood samples were collected. Groups were identified as group 1 (n = 10): control group; normal rat ration containing wheat, group 2 (n = 10): gluten-free diet, group 3 (n = 10): ration containing medium level of gluten (normal rat diet+6% vital gluten) and group 4 (n = 10): ration containing high level of gluten (normal rat diet+12% vital gluten). In groups 3 and 4, high-density lipoprotein was found to be higher than the other 2groups. However, when group 2 results were compared to the other groups; the highest T3, T4, creatinine and B12 levels and the lowest gluten-specific IgE level were observed. alanine aminotransferase and aspartate aminotransferase levels were found to be higher in group 1 compared to the other 3 groups. No statistically significant difference was detected between the groups in terms of other parameters. This study provides evidence that a gluten-containing diet does not cause weight gain, has no diabetogenic effect, and also does not adversely affect general health in relation to hematological, biochemical, and various endocrinological parameters.

The Effects of Alpha Lipoic Acid on Oxidative Stress, Lipid Profile, and Blood Glucose Levels in Type 2 Diabetic Male Sprague Dawley Rats

Objective: To determine the effect of Alpha Lipoic Acid (ALA) on blood glucose, lipid profile, and oxidative stress in streptozotocin-induced type II diabetic male Sprague Dawley rats.Study Design: Laboratory-based experimental study.Place and Duration of the Study: The study was carried out at the Physiology Research Lab, Army Medical College, Rawalpindi, Pakistan, from 20th January 2021 to 24th June 2021.Methods: Thirty Sprague Dawley (SD) rats were divided into three equal groups. Group I was given a normal standard rat diet. In Groups II and III after feeding a diet rich in fat and calories for 2 weeks, after feeding a diet rich in fat and calories for 2 weeks, a single low dose of streptozotocin was injected for Type 2 Diabetes Mellitus (T2DM) induction. Alpha Lipoic Acid 30 mg/kg body weight/day was administered intraperitoneally in Group III for 01 weeks after the development of T2DM.Results: The blood glucose, lipid profile, and serum Malondialdehyde levels were deranged in the diabetic group. After Alpha Lipoic Acid supplementation, the blood glucose levels, Serum MDA, and levels of triglycerides, cholesterol, and Low Density Lipoproteins decreased, whereas High Density Lipoproteins level were significantly raised (p &lt;0.001) in group III as compared to the diabetic group II. Conclusion: Treatment with Alpha Lipoic Acid reduces oxidative stress and improve reduces oxidative stress and improves glycemic and lipid profiles in T2DM rats.&#x0D; How to cite this: khan BU, Arshad S, Ikram F, Yousef I, Naizi I, Ismaeel M. The Effects of Alpha Lipoic Acid on Oxidative Stress, Lipid Profile and Blood Glucose Levels in Type 2 Diabetic Male Sprague Dawley Rats. Life and Science. 2024; 5(1): 89-94. doi: http://doi.org/10.37185/LnS.1.1.405

Cladophora glomerata Kützing extract exhibits antioxidant, anti-inflammation, and anti-nitrosative stress against impairment of renal organic anion transport in an in vivo study.

Cladophora glomerata extract (CGE), rich in polyphenols, was reported to exhibit antidiabetic and renoprotective effects by modulating the functions of protein kinases-mediated organic anion transporter 1 (Oat1) and 3 (Oat3) in rats with type 2 diabetes mellitus (T2DM). Nevertheless, the antioxidant effects of CGE on such renoprotection have not been investigated. This study examined the mechanisms involved in the antioxidant effects of CGE on renal organic anion transport function in an in vivo study. Diabetes was induced in the rats through a high-fat diet combined with a single dose of 40 mg/kg body weight (BW) streptozotocin. Subsequently, normal-diet rats were supplemented with a vehicle or 1,000 mg/kg BW of CGE, while T2DM rats were supplemented with a vehicle, CGE, or 200 mg/kg BW of vitamin C for 12 weeks. The study evaluated the general characteristics of T2DM and renal oxidative stress markers. The renal organic transport function was assessed by measuring the para-aminohippurate (PAH) uptake using renal cortical slices and renal inflammatory cytokine expression in the normal diet (ND) and ND + CGE treated groups. CGE supplementation significantly reduced hyperglycemia, hypertriglyceridemia, insulin resistance, and renal lipid peroxidation in T2DM rats. This was accompanied by the normalization of high expressions of renal glutathione peroxidase and nuclear factor kappa B by CGE and vitamin C. The renal anti-inflammation of CGE was evidenced by the reduction of tumor necrosis factor-1α and interleukin-1β. CGE directly blunted sodium nitroprusside-induced renal oxidative/nitrosative stresses and mediated the PAH uptake in the normally treated CGE in rats was particularly noteworthy. These data also correlated with reduced nitric oxide production, highlighting the potential of CGE as a therapeutic agent for managing T2DM-related renal complications. These findings suggest that CGE has antidiabetic effects and directly prevents diabetic nephropathy through oxidative/nitrosative stress pathways.

RYGB surgery has modest effects on intestinal morphology and gut hormone populations in the bypassed biliopancreatic limb but causes reciprocal changes in GLP-2 and PYY in the alimentary limb.

Roux-en-Y gastric-bypass (RYGB) induced alterations in intestinal morphology and gut-cell hormone expression profile in the bypassed biliopancreatic-limb (BPL) versus the alimentary-limbs (AL) are poorly characterised. This pilot study has therefore explored effects following RYGB in high-fat-diet (HFD) and normal-diet (ND) rats. Female Wistar rats (4-week-old) were fed HFD or ND for 23-weeks prior to RYGB or sham surgeries. Immunohistochemical analysis of excised tissue was conducted three-weeks post-surgery. After RYGB, intestinal morphology of the BPL in both HFD and ND groups was unchanged with exception of a small decrease in villi width in the ND-RYGB and crypt depth in the HFD-RYGB group. However, in the AL, villi width was decreased in ND-RYGB rats but increased in the HFD-RYGB group. In addition, crypt depth decreased after RYGB in the AL of HFD rats. GIP positive cells in either limb of both groups of rats were unchanged by RYGB. Similarly, there was little change in GLP-1 positive cells, apart from a small decrease of numbers in the villi of the BPL in HFD rats. RYGB increased GLP-2 cell numbers in the AL of ND-RYGB rats, including in both crypts and villi. This was associated with decreased numbers of cells expressing PYY in the AL of ND-RYGB rats. The BPL appears to maintain normal morphology and unchanged enteroendocrine cell populations despite being bypassed in RYGB-surgery. In contrast, in the AL, villi area is generally enhanced post-RYGB in ND rats with increased numbers of GLP-2 positive cells and decreased expression of PYY.

Altered serum metabolome associated with vascular calcification developed from CKD and the critical pathways.

Vascular calcification (VC) is more likely to be detected in the chronic kidney disease (CKD) population. The mechanism of VC development from CKD is different from that for simple VC and has always been a major research area. The aim of this study was to detect alterations in the metabolome during development of VC in CKD and to identify the critical metabolic pathways and metabolites involved in its pathogenesis. Rats in the model group were given an adenine gavage combined with a high-phosphorus diet to imitate VC in CKD. The aorta calcium content was measured and used to divide the model group into a VC group and non-vascular calcification group (non-VC group). The control group was fed a normal rat diet and given a saline gavage. Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to determine the altered serum metabolome in the control, VC, and non-VC groups. The identified metabolites were mapped into the Kyoto Encyclopedia of Genes and Genomes (KEGG) database (https://www.genome.jp/kegg/) for pathway and network analyses. There were 14 metabolites that changed significantly in the VC group, with three metabolic pathways playing critical roles in the pathogenesis of VC in CKD: steroid hormone biosynthesis; valine, leucine and isoleucine biosynthesis; and pantothenate and CoA biosynthesis. Our results indicated changes in the expression of steroid sulfatase and estrogen sulfotransferase, and down-regulation of the in situ synthesis of estrogens in the VC group. In conclusion, the serum metabolome alters significantly during the pathogenesis of VC in CKD. The key pathways, metabolites, and enzymes we identified are worth further study and may become a promising therapeutic target for the treatment of VC in CKD.

PROPERTIES OF FATIGUE BETWEEN SLOW AND FAST MUSCLES OF MALE AND FEMALE DIABETIC RATS

Background: The metabolic disorder of Type 2 Diabetes Mellitus (T2DM) has deleterious effects on skeletal muscle contractile functions. This study aimed to compare parameters of fatigue between slow and fast skeletal muscles of male and female type 2 diabetic Sprague-Dawley rats. Methodology: This was a quasi experimental study conducted at Army Medical College Rawalpindi and National Institute of Health, Islamabad. Forty Sprague Dawley rats in good health were split into groups I (Control) and II (Diabetics) of 20 rats each. Each group had 10 male and 10 female rats. Diabetic groups were given intra-peritoneal streptozotocin (STZ), 35 mg/Kg body weight on 15th day. Control groups were fed a normal diet and diabetic rats were given diet with high fat. On 21st day body weight, blood glucose and triglyceride/high density lipoprotein ratio were estimated to confirm extraction of type 2 diabetes mellitus. Intact Soleus and Extensor Digitorium Longus muscles were removed and fixed in organ bath system having Krebs-Ringer buffer solution and connected to data acquisition unit (iWorx®) to study their fatigability parameters. Independent samples t-test was used for statistical analysis. Results: Slow and fast skeletal muscles in diabetic rats showed reduction in resistance to and recovery from fatigue. Fatigue parameters between male and female diabetic rats revealed no significant differences. Conclusion: Fatigue parameters do not differ between male and female diabetic rats. Pak J Physiol 2023;19(1):7?10

Is oxidative stress involved in the hepatic inflammatory response to apical periodontitis? A comparative study in normal and hyperlipidaemic rat.

The aim of the study was to explore the involvement of oxidative stress (OS) in the hepatic inflammation induced by apical periodontitis (AP). Periapical, systemic and hepatic reaction to AP under hyperlipidaemia was also investigated. A total of 16 male Sprague-Dawley rats were fed with a hyperlipidaemic diet (HD) whereas another 16 rats with a normal diet (ND). After 9 weeks, the first molars of the right maxilla and mandible of 8 HD and 8 ND rats were exposed to induce AP (ND, ND + AP, HD and HD + AP group). After 5 weeks, rats were euthanized, the haematological tissue was collected directly from the heart, and serum levels of inflammatory cytokines were measured. Liver tissue was analysed by haematoxylin-eosin and Masson staining, and reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect mRNA expression of inflammatory cytokines. Serum, periapical, and hepatic OS parameters including total oxidant status (TOS), total antioxidant capacity (TAOC) and oxidative stress index (OSI) were measured by enzyme-linked immunosorbent assay (ELISA). The area of AP lesion in the right maxilla or mandible was radiographically assessed. Student's t-test was performed on the periapical data. A one-way analysis of variance and the Kruskal-Wallis test were analysed for others. The HD + AP group had a larger AP lesion in the maxilla, compared with the ND + AP group (p < .05). The ND + AP group presented higher serum interleukin (IL)-18, IL-1β, TOS, OSI levels, lower serum TOAC levels, higher hepatic tumour necrosis factor (TNF)-α mRNA expression and higher hepatic TOS, and OSI levels, compared with the ND group (p < .05). The HD + AP group had lower serum IL-4 level, higher serum IL-1β level, and higher hepatic IL-6 and transforming growth factor (TGF) -β1 mRNA expression, compared with the HD group (p < .05). Apical periodontitis could activate systemic and liver inflammation by promoting serum IL-18, 1L-1β, TOS and OSI expression, enhancing hepatic TOS and OSI expression and inhibiting serum TOAC expression. AP under hyperlipidaemia led to more profound periapical bone destruction in the maxilla and elicit systemic and liver inflammatory responses through elevating serum levels of IL-1β, descending serum IL-4 level and improving hepatic IL-6 and TGF-β1 expression.

Evaluation of flaxseed lignan-enriched extract targeting autophagy, apoptosis, and hedgehog pathways against experimentally induced obesity.

This research investigated secoisolariciresinol diglucoside (SDG) flax extract effects on apoptosis, hedgehog (Hh), autophagy, and the anti-oxidation process in experimentally induced obesity. Forty rats were separated into two sets regarding either receiving a normal balanced diet or a high-fat diet (HFD) and then distributed into four groups: GI: The control group had a regular diet for 12 weeks. GII: animals received a high-fat meal and saline by gastric gavage. GIII: HFD obese rats treated with SDG extract orally (10 mg/kg/b.w.) and 1.18 mg SDG/kg in the diet for 4 weeks GIV: Normal balanced diet rats received SDG extract orally (10 mg/kg/b.w.) and 1.18 mg SDG/kg of chow for 12 weeks in addition to their regular balanced diet. The administration of SDG extract exhibited a significant drop in body weight, glucose, lipid profile, and leptin compared to the obese group. It also improved the antioxidant levels (lowering the levels of malondialdehyde while increasing the total antioxidant capacity) and anti-inflammatory status (decreasing interleukin-6 and tumor necrosis factor-alpha). SDG extract downregulates the expression of HH genes (protein patched homolog 1, Hh-interacting protein, glioma-associated oncogene homolog 1, and smoothened receptor) in conjunction with the modulation of autophagy genes and apoptotic proteins. SDG extract showed improved anti-inflammatory and antioxidant status and downregulated the expression of HH genes while modulating autophagy genes and apoptotic proteins among obese rats, suggesting that it may be used to avert and manage obesity and its correlated complications by modulating oxidation, inflammation, autophagy, and apoptosis. Advanced future research on the SDG autophagy pathway to address obesity and its complications is mandatory.

Ethanol Extracts of Eriobotrya japonica (Loquat) Seeds, Leaves, and Fruits Have Anti-obesity and Hypolipidemic Effects in Rats

Background: Obesity is a serious public health problem contributing to development of several diseases, including hyperlipidemia, hyperglycemia, and hypertension. The plant Eriobotrya japonica (loquat) has been used in traditional Chinese medicine to treat many ailments and traditional healers used it to reduce weight. Objectives: To examine the potential anti-obesity and hypolipidemic effects of ethanol extract of loquat in rats. Materials and Methods: Loquat leaves, fruits, or seeds were extracted with ethanol. About 96 Wistar male rats were fed either a normal rat diet (normal control group; group 1) or a high-fat diet (HFD) for 12 weeks (obese; groups 2−12). Obese rats were divided into11 groups as follows: (obese control: group 2) (obese positive control which received the hypolipidemic reference drug atorvastatin: group 3). Groups (4−6), (7−9), and (10−12) were given seed, leaf, or fruit extract, respectively, at 40,100, and 400 mg/kg. Body weight, serum glucose, lipid profile, creatinine, liver enzymes, albumin, and total protein were measured weekly. Results: HFD consumption significantly increased body weight and serum total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL), very-low density lipoprotein (VLDL), and glucose and decreased HDL compared to rats fed the normal diet. HFD also increased serum glutamic-oxaloacetic transaminase (GOT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) and creatinine but decreased serum albumin and total protein. Administration of E. japonica seed, leaf, or fruit extract significantly decreased body weight, TC, TGs, LDL, VLDL, glucose, liver, and renal enzymes but increased HDL, albumin, and total protein levels. Conclusion: E. japonica seed, leaf, and fruit ethanol extract regulates body weight gain, has hypolipidemic properties, and positively affects liver and kidney enzymes.

Calorie restriction, but not Roux-en-Y gastric bypass surgery, increases [3 H] PK11195 binding in a rat model of obesity.

Roux-en-Y gastric bypass surgery (RYGB) remains an effective weight-loss method used to treat obesity. While it is successful in combating obesity, there are many lingering questions related to the changes in the brain following RYGB surgery, one of them being its effects on neuroinflammation. While it is known that chronic high-fat diet (HFD) contributes to obesity and neuroinflammation, it remains to be understood whether bariatric surgery can ameliorate diet-induced inflammatory responses. To examine this, rats were assigned to either a normal diet (ND) or a HFD for 8 weeks. Rats fed a HFD were split into the following groups: sham surgery with ad libitum access to HFD (sham-HF); sham surgery with calorie-restricted HFD (sham-FR); RYGB surgery with ad libitum access to HFD (RYGB). Following sham or RYGB surgeries, rats were maintained on their diets for 9 weeks before being euthanized. [3 H] PK11195 autoradiography was then performed on fresh-frozen brain tissue in order to measure activated microglia. Sham-FR rats showed increased [3 H] PK11195 binding in the amygdala (63%), perirhinal (60%), and ectorhinal cortex (53%) compared with the ND rats. Obese rats who had the RYGB surgery did not show this increased inflammatory effect. Since the sham-FR and RYGB rats were fed the same amount of HFD, the surgery itself seems responsible for this attenuation in [3 H] PK11195 binding. We speculate that calorie restriction following obese conditions may be seen as a stressor and contribute to inflammation in the brain. Further research is needed to verify this mechanism.

Effect of gut microbiota and metabolites in normal rats treated with large yellow croaker (Larimichthys crocea) roe phospholipids

Phospholipids derived from marine source has been widely demonstrated with hypolipidemic effect by establishing sub-healthy animal models. However, the health benefits of large yellow croaker roe phospholipids (LYCRPLs) on normal diet (ND) rats remains poorly understood. The aim of this study was to investigate the possible effect exhibited by ND rats' gut microbiota and metabolism response to LYCRPLs. Three group rats were fed diets supplemented with ND and LYCRPLs for 8 weeks, respectively. The rats’ food intake, body weight, liver and epididymal adipose tissue and organ weight were initially analyzed, then explored the effect of LYCRPLs in gut microbiota and metabolism. The results revealed that LYCRPLs can positively regulated the gut microbiota by increasing the relative abundance of Firmicutes, Lactobacillus, andLachnospiraceae_NK4A136 group etc., and decreased harmful bacteria (Proteobacteria). Moreover, the intervention of LYCRPLs also significantly down-regulated the Citrate cycle (TCA cycle), Fat digestion and absorption, Carbohydrate digestion and absorption, Protein digestion and absorption pathways of normal rats, which indicates that LYCRPLs possess potential ability to regulate glycolipid metabolism. These findings reveal that LYCRPLs can be used as a gut microbiota manipulator to regulate the glycolipid metabolism for health promotion, which offers new prospects for LYCRPLs as a functional ingredient for the food industry.

Cytochrome P450 2E1 gene knockout or inhibition prevents obesity induced by high-fat diet via regulating energy expenditure

Cytochrome P450 2E1 (CYP2E1), an important member of the CYP metabolic enzyme family in the liver, regulates the disposal of drugs and the biotransformation of endogenous substances. Although previous studies have found that CYP2E1 is related to energy metabolism, the role of CYP2E1 in energy homeostasis remains unclear. Herein this study shows that the deletion of Cyp2e1 gene in rats can prevent obesity, fatty liver and insulin resistance induced by high-fat diet. Mechanism studies uncover that Cyp2e1 deficiency not only increases the expression of thermogenic genes in brown adipose tissue (BAT) and subcutaneous adipose tissue (SAT), but also promotes fatty acid metabolism in the liver and BAT. In particular, Cyp2e1 deficiency elevates energy expenditure through an increase of liver-generated acylcarnitines, which promote BAT thermogenesis and increase β-oxidation. Interestingly, disulfiram as a CYP2E1 inhibitor can also prevent obesity induced by high-fat diet in normal rats. In general, this study explains the relationship between CYP2E1 and energy metabolism, and provides a new perspective for the prevention and treatment of obesity.

PRELIMINARY aTOXICOLOGICAL INVESTIGATION OF ENTADA PURSAETHA SEED OIL

High density lipoprotein (HDL), low density lipoprotein (LDL) and triglyceride (TG) are collectively referred as lipids; their levels could be modified by the type and amount of oil in human diet. In this study, Entada pursaetha seed oil (EPO) was evaluated for its toxicity status in order to determine its suitability/potential for human diet. Oil from E. pursaetha seeds used for this study was extracted with n-hexane. Fifteen wistar rats, distributed into three groups of five rats each, were fed with groundnut oil diet (positive control group), EPO diet (test group) and normal rat diet (control group) for eight weeks after which the animals were sacrificed. During the study period, clinical observation of the rats were noted, body weight of the rats was taken on a weekly basis while haematological analysis of the blood and histopathological evaluation of the heart of the rats were carried out at the end of the study. Clinical observation of the rats revealed that the rats did not show any untoward signs throughout the study period. Body weight increase of the rats was found to be steady and no mortality of any of the rats was recorded for all the groups. There was no significant difference in the haematological analysis result for the blood of the rats in the test and control groups and none of them was anaemic; this is nutritionally significant. The result of the histopathological analysis of the heart of the rats for total cholesterol and triglyceride indicated that rats fed with EPO had higher total cholesterol and triglyceride than the control group rats. EPO seemingly has potential of serving nutritional purposes but must be subjected to refining before this can probably be possible. It can however find very wide application industrially.

Chitosan Oligosaccharide Ameliorates Kidney Injury by Improving Intestinal Barrier Dysfunction and Lipid Metabolism in Obese‐insulin Resistant Rats

IntroductionObesity remains a global health problem. High‐fat diet (HFD) consumption increases the risk of type 2 diabetes and initiates kidney injury. Chitosan Oligosaccharide (COS) provides anti‐obesity effects through several mechanisms. However, the effects of COS on preventing obesity‐related kidney injury in obese‐insulin resistance have not been studied. A novel action of COS in activating intestinal tight junction assembly was reported in in vitro via calcium sensing receptor‐mediated AMP‐activated protein kinase (CaSR/AMPK) activation. HFD‐induced gut dysbiosis is related with intestinal barrier dysfunction and systemic low‐grade inflammation. Therefore, AMPK activation might be a therapeutic target for preventing obesity‐related complications. Here, we explored the protective effects of COS in obesity‐induced kidney dysfunction and the involved molecular mechanisms. We hypothesized that COS might exert renoprotection against obesity‐induced kidney injury through increasing intestinal barrier integrity and lipid excretion.MethodsMale Wistar rats were fed with HFD for 16 weeks to induce obesity. Next, HFD rats were randomly divided into 4 groups: HFD, HFD treated with COS 5 or 10 mg/kg/day (COS5 or COS10) and HFD treated with metformin 30 mg/kg/day (MET). The interventions were orally treated for 8 weeks. At the end of experiment, blood, feces, intestinal and renal tissue samples were collected for further investigations.ResultsAfter 16 weeks of high‐fat diet feeding, obesity and glucose intolerance were presented in HFD compared to normal diet (ND) rats, as indicated by the significant increases in body weight (BW), plasma cholesterol and total area under the curve for glucose (TAUCg). Kidney injury were observed at week 24, as shown by elevated kidney injury score and serum creatinine. Treatment with COS5 or COS10 significantly decreased BW, hypercholesterolemia, glucose intolerance and kidney dysfunction. Interestingly, COS10 markedly increased fecal lipid excretion compared with HFD and MET. In addition, intestinal CaSR, p‐AMPK/AMPK and tight junction protein claudin‐1 expressions were downregulated in HFD which were upregulated by COS10 and MET. Renal TNFαR activation and increased proinflammatory cytokines were detected in HFD. Moreover, renal apoptosis markers, Bcl‐2‐associated X protein (Bax) and cleaved caspase‐3, were increased, along with the suppressing of anti‐apoptotic B‐cell lymphoma‐2 (Bcl‐2) in HFD. Treatment with COS10 or MET markedly alleviated renal inflammation and apoptosis.ConclusionCOS exerted renoprotection through attenuating renal inflammation and apoptosis as a result of improving intestinal barrier via CaSR/AMPK activation and lipid absorption in obese rats. Therefore, COS might be an effective new dietary supplement for treating obesity and its related complications in clinical use.

Evaluation of the nutrient composition and hepatotoxic potential of Thaumatococcus danielli

The aim of this work was to evaluate the nutritional and hepatotoxic potential of leaf of T. danielli. Freshly harvested leaves of T. danielli was dried at room temperature, ground to fine powder. 500 g of powdered plant sample was soaked in 2 litres of 70% methanol for 72 hrs. The resulting extract was filtered and filtrate concentrated. Twenty adult male albino rats were divided into 4 groups of 5 rats per group. · Group I: Normal control was fed with only normal rat diet and water ad libitum. · Group II: Rats were administered with 200 mg/kg b.w of extract of T.danielli leaf orally. · Group III: Rats were administered with 400 mg/kg b.w of methanol extract of T.danielli leaf orally. · Group IV: Rats were administered with 600 mg/kg b.w of methanol extract of T.danielli leaf orally. Nutrient composition of the leaf of T. danielli was determined using standard procedures. The proximate analysis on the leaf of the said plant revealed the presence of moisture, ash, fat, protein, fibre and carbohydrate with fat being more abundant (17.30±1.28%) than every other components and carbohydrate the least abundant (8.29±0.20%). However, analysis on the mineral composition, revealed the presence of calcium, phosphorus, potassium, zinc, sodium and iron. While calcium (7.20±0.23 g/ 100 g) was reportedly the most abundant of all elements, sodium was the least (0.40±0.03 g/ 100g). Evaluation of the vitamin composition of the leaf of T. danielli revealed the presence of vitamins A, B1, B3, B5, B6 and B12. B12 was the most abundant (8.32±0.42 g/ 100g) of the vitamins. The activity of serum hepatomarkers evaluated was not significantly (P&gt;0.05) different from that reported on the control following oral administration of aqueous extract of T. danielli. In conclusion, the leaf of T. danielli contains vital nutrients and has no hepatotoxic effect.

Modulatory effect of fermented Tetracarpidium conophorum (African walnut) supplemented diet on cadmium-induced toxicity in rats

Tetracarpidium conophorum (African Walnut) is a plant with acclaimed multi-therapeutic properties in different parts of the plant. This research investigated the effect of fermented walnut supplemented diet on cadmium-induced toxicity in the liver and brain of rats. Twenty male Wistar rats were divided into four groups of five animals each weighing between 90-140 g. Group 1 received 5 mg/kg body weight cadmium chloride (CdCl2) and normal rat feed. Group 2 received a normal rat diet while groups 3 and 4 received 5 mg/kg body weight of cadmium chloride, and 5% and 10% walnut supplemented feed respectively. Cadmium (Cd) was administered daily for 6 weeks by oral intubation. Rats were sacrificed 24 hrs after the final treatment. Cd exposure elicited increased activities of Acetylcholinesterase, Superoxide dismutase, Catalase as well as elevated Glutathione levels. In addition, Cd exposure caused increases in rat plasma cholesterol and triglyceride concentration. The fermented walnut supplemented diet restored some rats’ biochemical parameter to near normal comparable to control. Our study shows that walnut supplemented food could substantially moderate Cd-induced toxicity in rat liver and brain while providing health and nutritional benefits. Hence, it could be useful for occupationally exposed individuals as a dietary intervention to reduce adverse health effects.

High‐fat diet reduced dendritic spine density, but it did not affect cognitive function in spontaneous diabetic torii rats

Diabetes is a known risk factor for dementia, several factors are involved in the pathogenesis of diabetes including genetic predisposition, and high calorie diet consumption. We previously reported that long-term high-fat diet (HFD) consumption led to prediabetes, which associated with cognitive impairments. However, the effects of long-term HFD consumption on metabolic and brain function in genetically type 2 diabetes (T2DM) model have not been investigated. Therefore, we hypothesized that long-term HFD consumption aggravates metabolic and cognitive impairments in T2DM rats. Sixteen Spontaneous Diabetic Torii (SDT) rats, which is a genetically engineered T2DM rats, and eight wild type (WT) rats were used. At the age of 8 weeks old, SDT rats were divided into two dietary groups either normal diet or HFD feeding for 12 weeks. WT rats were received a normal diet entire the study. At 20 weeks old, metabolic parameters, the hippocampal dependent cognitive function using novel object location (NOL) test, and hippocampal dendritic spine density were determined. Our data demonstrated that, at 20 weeks old, SDT rats in both dietary groups exhibited their diabetic characters as indicated by hyperglycemia, hypoinsulinemia, and insulin insensitivity. HFD feeding did not aggravate diabetic status, but it significantly induced body weight gain, visceral fat deposition, hypertriglyceridemia, and hypercholesterolemia (as shown in Figure 1). Unexpectedly, hippocampal dependent cognitive impairments were not observed in both normal diet and HFD-fed SDT rats, when compared with WT rats (Figure 1). However, brain mitochondrial dysfunction and dendritic spine loss were observed in both dietary groups of SDT rats. Interestingly, the reduction of dendritic spine density was greater in HFD-fed SDT rats than normal diet-fed SDT rats (Figure 1). Long-term HFD consumption induced truncal obesity, dyslipidemia, and reduced dendritic spine density in SDT rats, but it did not affect hippocampal dependent cognitive function. It is possible that the duration of HFD feeding was insufficient to promote cognitive impairments in genetically T2DM rats.