Kidney Of Diabetic Rats Research Articles

Hyperbaric oxygen therapy prevents epithelial atrophy in distal tubules and TGF-β1 overexpression in diabetic rat kidneys.

Diabetic nephropathy (DN) is one of the most relevant and prevalent microvascular complications associated with Diabetes Mellitus. In recent years, hyperbaric oxygen therapy (HBO) has been used to mitigate tissue damage caused by hypoxia, thereby attenuating inflammatory processes. This study aimed to explore morphological aspects associated with DN in rats subjected to HBO. Forty-eight Wistar rats were divided into the following groups: C (normoglycemic animals), n = 12; C + HBO (normoglycemic animals submitted to HBO), n = 12; D (diabetic animals) n = 12; D + HBO (diabetic animals submitted to HBO), n = 12. The C + HBO and D + HBO groups were daily treated with HBO at 2.5 atmospheres absolute pressure (ATA) for 60min, 5 days a week, for 5 weeks. Kidneys were collected for assessment of structural changes in the tissue parenchyma, assessment of renal fibrosis and renal protein expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1). Our results showed that group D had hyperglycemia and weight loss, and that there was also an increase in the renal corpuscle, Bowman's space, and distal tubular epithelium, as well as accumulation of collagen. HBO administration effectively prevented glomerular hypertrophy and attenuated the expression of TNF-α and TGF-β1. It also positively affected renal tubules, inhibiting the development of tubular atrophy. These findings suggest that HBO was effective in attenuating the initial alterations observed in DN.

Effect of cuproptosis on acute kidney injury after cardiopulmonary bypass in diabetic patients

BACKGROUND Cardiopulmonary bypass (CPB) is a common procedure in cardiac surgery. CPB is a high-risk factor for acute kidney injury (AKI), and diabetes is also such a factor. Diabetes can lead to copper overload. It is currently unclear whether AKI after CPB in diabetic patients is related to copper overload. AIM To explore whether the occurrence of CPB-AKI in diabetic patients is associated with cuproptosis. METHODS Blood and urine were collected from clinical diabetic and non-diabetic patients before and after CPB. Levels of copper ion, lactate, glucose, heat shock protein-70 (HSP-70), and dihydrolipoamide dehydrogenase (DLAT) were determined. A diabetic rat model was established and CPB was performed. The rats were assessed for the development of CPB-AKI, and for the association of AKI with cuproptosis by detecting copper levels, iron-sulfur cluster proteins and observation of mitochondrial structure by electron microscopy. RESULTS CPB resulted in elevations of copper, lactate, HSP-70 and DLAT in blood and urine in both diabetic and non-diabetic patients. CPB was associated with pathologic and mitochondrial damage in the kidneys of diabetic rats. Cuproptosis-related proteins also appeared to be significantly reduced. CONCLUSION CPB-AKI is associated with cuproptosis. Diabetes mellitus is an important factor aggravating CPB-AKI and cuproptosis.

Flavonoid-rich fraction of Monodora tenuifolia Benth seeds improves antioxidant status in male Wistar rats with streptozotocin-induced Diabetes mellitus

BackgroundOxidative stress is a disruption in the balance between free radicals and the body's natural defenses. This study investigated the modulatory effect of a flavonoid-rich fraction of Monodora tenuifolia seed (FRFMTS) on oxidative stress and antioxidant enzymes in diabetic Wistar rats. The plant seeds were collected, and identified then, hydro-ethanolic extract was obtained with 80 % (v/v) ethanol and partitioned with solvents to obtain the FRFMTS. Diabetes mellitus was induced with a single dose of 40 mg/kg bwt streptozotocin and the rats were treated according to their grouping; group 1: non-diabetic control, groups 2 and 3: non-diabetic treated with 25 mg/kg FRFMTS and 50 mg/kg FRFMTS, respectively. Group 4: diabetic control group, groups 5 and 6: diabetic groups treated with 25 mg/kg and 50 mg/kg FRFMTS, respectively, while group 7: diabetic treated with 6.67 mg/kg metformin. Antioxidant status, oxidative stress biomarkers and activities of antioxidant enzymes were determined in plasma, heart, and kidney tissues using established procedures. ResultsPlasma total antioxidant status (TAS) was increased significantly (p < 0.05) in diabetic rats upon treatment with 25 mg/kg FRFMTS (70.4 %), while 50 mg/kg FRFMTS increased TAS by 70 %. The activities of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in the plasma, heart, and kidney of diabetic rats significantly decreased (61.3 %, 58.8 % and 31.4 % respectively) while lipid peroxidation (LPO) was elevated when compared with normal control groups. Flavonoid-rich fraction of M. tenuifolia at 25 mg/kg bwt and 50 mg/kg bwt significantly increased the activity GPx enzyme by 32.3 % and 72 % in plasma, while there was no significant differences in both kidney and heart of diabetic rats when compared with diabetic control groups. The treatment of diabetic rats with 25 mg/kg FRFMTS and 50 mg/kg FRFMTS improved SOD activity in the plasma (51.5 % and 69.8 %), heart (32.3 % and 27.6 %) and kidney (31.4 % and 27.1 %) respectively, and CAT activity in plasma (44.2 % and 57 %), heart (28.6 % and 60 %) and kidney (69.6 % and 76.7 %) respectively. The concentration of malondialdehyde (MDA) in lipid peroxidation assay in the heart and kidney of diabetic rats treated with 25 mg/kg FRFMTS and 50 mg/kg FRFMTS reduced significantly by (62.5 % and 71.1 % in heart), while 50 mg/kg FRFMTS significantly reduced MDA in kidney by 43.8 %. ConclusionsThe results showed that FRFMTS reduces oxidative stress and enhances the activities of antioxidant enzymes in STZ-diabetic Wistar rats. As such, FRFMTS could be useful in the management of oxidative stress-mediated diabetic complications.

AMELIORATION OF LIVER AND KIDNEY FUNCTION PARAMETERS IN ALLOXAN-INDUCED DIABETIC RATS TREATED WITH 3-[2-(1,5-Dimethyl-3-oxo-2-Phenyl-2,3-Dihydro- 1H-Pyrazol-4-yl) Hydrazinylidene]-1-Phenylbutanedione, and its Ni(II) Complex.

This hydrazone: 3-[2-(1,5-Dimethyl-3-oxo-2-Phenyl-2,3-Dihydro-1H-Pyrazol-4-yl) Hydrazinylidene]-1-Phenylbutanedione (HL), and its Ni (II) Complex ([Ni(HL)2]Cl2) have been reported to possess hypoglycaemic property but the effects of their use on kidney and liver functions in diabetic animals have not been investigated. The study investigated some biochemical parameters in the liver and kidney of alloxan-induced diabetic rats treated with these hydrazone compounds. Diabetes was induced by a single intraperitoneal dose of alloxan (150 mg/kg). Data showed that these compounds induced a significant decrease in serum glucose levels in the diabetic rats. Diabetic rats were administered orally with compounds for fourteen days after which some biochemical indices in the serum, liver and kidney were measured and compared with the control. Serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, total protein and creatinine of untreated diabetic group was significantly elevated when compared with the normal control group. The ALP, AST concentrations of diabetic rats treated with low and high doses of HL was observed to be non-significantly (p &gt; 0.05) higher compared with rats in the normal control group A. A significantly (p &lt; 0.05) decrease in the ALT, AST and ALP concentrations of diabetic rats treated with 200 and 400 mg/kg b.w. of HL and [Ni(HL)2]Cl2 were observed when compared with untreated rats in group B. These results suggest that administration of these compounds to diabetic rats did not have any adverse effect on the liver and kidney functions in rats showing that the compounds are not toxic to man.

Therapeutic role of Arabic gum against nicotinamide/streptozotocin-induced diabetes and nephropathy in Wistar rats

Background Chronic kidney disease is mainly caused by diabetic nephropathy and also causes a lot of suffering and death for people with diabetes, as one of the worst long-term complications. Arabic gum (AG) has been reported to have antioxidant, hypolipidemic and hypoglycemic effects. Objective The goal of this study was to scrutinize the antioxidant and anti-inflammatory roles of AG against nicotinamide (NA)/streptozotocin (STZ)-induced diabetic nephropathy in Wistar rats. Materials and methods The experiment involved three groups of 18 adult male Wistar rats (six each). The normal control group received 0.9% NaCl orally for 8 weeks. The diabetic group received NA intraperitoneal injection (120 mg/kg b.w.) followed by 60 mg/kg body weight (bw) STZ in citrate buffer (pH 4.5) after 15 min. After confirming the induction of diabetes, animals received 0.9% NaCl orally for 8 weeks. The AG-treated diabetic group received 20 mg AG/kg bw/day orally for 8 weeks after diabetes induction. Results and conclusion Diabetic rats exhibited hyperglycemia which was confirmed by increased levels of serum fasting glucose and fructosamine. Elevated serum urea, creatinine, uric acid, cystatin c, and sodium levels were noticed in the serum of diabetic rats while potassium levels were markedly reduced reflecting nephropathy. Oxidative stress was evident in the diabetic kidney, as indicated by increased malondialdehyde (MDA) and decreased reduced glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD). AG administration ameliorated elevated fasting blood glucose and serum fructosamine levels as well as the kidney function parameters in serum. AG also attenuated oxidative stress and increased antioxidant capacity in the diabetic kidney. Immune-inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), and tumor suppressor protein (p53) expression were significantly upregulated in diabetic rats, but AG produced a downregulation of them. Thus, AG possesses an antidiabetic effect and has a nephropreventive effect that was manifested by a decrease of urea, creatinine, uric acid, cystatin c and sodium. AG also has anti-inflammatory and antioxidant effects and minimizes histopathological alterations in the kidneys of diabetic rats. Despite these ameliorative effects, the efficacy and safety of AG as an adjunct drug for diabetic kidney disease needs to be validated by more scientific research.

Astaxanthin attenuates diabetic kidney injury through upregulation of autophagy in podocytes and pathological crosstalk with mesangial cells

Objectives: Astaxanthin (ATX) is a strong antioxidant drug. This study aimed to investigate the effects of ATX on podocytes in diabetic nephropathy and the underlying renal protective mechanism of ATX, which leads to pathological crosstalk with mesangial cells.Methods: In this study, diabetic rats treated with ATX exhibited reduced 24-h urinary protein excretion and decreased blood glucose and lipid levels compared to vehicle-treated rats. Glomerular mesangial matrix expansion and renal tubular epithelial cell injury were also attenuated in ATX-treated diabetic rats compared to control rats.Results: ATX treatment markedly reduced the α-SMA and collagen IV levels in the kidneys of diabetic rats. Additionally, ATX downregulated autophagy levels. In vitro, compared with normal glucose, high glucose inhibited LC3-II expression and increased p62 expression, whereas ATX treatment reversed these changes. ATX treatment also inhibited α-SMA and collagen IV expression in cultured podocytes. Secreted factors (vascular endothelial growth factor B and transforming growth factor-β) generated by high glucose-induced podocytes downregulated autophagy in human mesangial cells (HMCs); however, this downregulation was upregulated when podocytes were treated with ATX.Conclusions: The current study revealed that ATX attenuates diabetes-induced kidney injury likely through the upregulation of autophagic activity in podocytes and its antifibrotic effects. Crosstalk between podocytes and HMCs can cause renal injury in diabetes, but ATX treatment reversed this phenomenon.

Ameliorative Effect of Justicia carnea Methanol Leaf Extract against Nephrotoxicity in Streptozotocin-Induced Diabetic Wistar Rats

This study investigated the antioxidant capabilities of methanol extract from Justicia carnea leaves in streptozotocin (STZ)-induced diabetic Wistar rats, emphasizing its nephroprotective potential. Thirty-six (36) Wistar albino rats were randomized into six (6) groups (n=6/group). Group 1 served as the normal control, while groups 2-6 were induced with diabetes using 50 mg/kg of STZ intraperitoneally. Group 2 remained untreated, group 3 received 50 mg/kg body weight of Metformin, and groups 4, 5, and 6 were administered 100, 200, and 500 mg/kg body weight of the methanol Justicia carnea extract, respectively. Parameters assessed included fasting blood glucose (FBG), body weight changes, acute toxicity, and oxidative stress markers. Acute toxicity testing indicated no deaths at 5000 mg/kg of the extract. The extract significantly lowered FBG levels in STZ-induced diabetic rats (p &lt; 0.05). The control group exhibited the highest weight gain compared to the treated groups (p &lt; 0.05). Treatment with the extract notably increased catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels, while decreasing malondialdehyde (MDA) concentrations (p &lt; 0.05) compared to diabetic controls. Overall, the methanol extract of Justicia carnea ameliorated oxidative stress in the kidneys of diabetic Wistar rats, suggesting its potential to mitigate nephrotoxicity associated with type I diabetes-induced kidney damage. These findings underscore its therapeutic promise in combating oxidative stress-related complications of diabetes.

SARS-CoV-2 Spike Protein Enhances Carboxypeptidase Activity of Angiotensin-Converting Enzyme 2.

In this study, we investigated whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein may modify angiotensin-converting enzyme 2 (ACE2) activity in the plasma, heart, kidney, liver, lung, and six brain regions (amygdala, brain stem, cortex, hippocampus, hypothalamus, and striatum) of diabetic and hypertensive rats. We determine ACE2 activity in the plasma and lysates of heart, kidney, liver, lung, and six brain regions. MLN-4760 inhibits ACE2 activity in the plasma and all organs. On the other hand, soluble ACE2 (sACE2) activity increased in the plasma of diabetic rats, and there was no change in the plasma of hypertensive rats. ACE2 activity was augmented in the liver, brain stem, and striatum, while it decreased in the kidney, amygdala, cortex, and hippocampus of diabetic rats. ACE2 activity increased in the kidney, liver, and lung, while it decreased in the heart, amygdala, cortex, and hypothalamus of hypertensive rats. We measured the ACE2 content via enzyme-linked immunosorbent assay and found that ACE2 protein levels increased in the heart, while it decreased in the plasma, kidney, brain stem, cortex, hippocampus, hypothalamus, and striatum of diabetic rats. ACE2 protein levels decreased in the brain stem, cortex, hippocampus, and hypothalamus of hypertensive rats. Our data showed that the spike protein enhanced ACE2 activity in the liver and lungs of diabetic rats, as well as in the heart and three of the brain regions (cortex, hypothalamus, and striatum) of hypertensive rats.

Ameliorative Effect of Pigeon Pea Leaves and Ginger Extract on Oxidative Stress Condition in Kidney and Liver of Experimental Diabetic Rats

Ameliorative Effect of Pigeon Pea Leaves and Ginger Extract on Oxidative Stress Condition in Kidney and Liver of Experimental Diabetic Rats

Lycopene in Combination with Insulin Triggers Antioxidant Defenses and Increases the Expression of Components That Detoxify Advanced Glycation Products in Kidneys of Diabetic Rats.

Biochemical events provoked by oxidative stress and advanced glycation may be inhibited by combining natural bioactives with classic therapeutic agents, which arise as strategies to mitigate diabetic complications. The aim of this study was to investigate whether lycopene combined with a reduced insulin dose is able to control glycemia and to oppose glycoxidative stress in kidneys of diabetic rats. Streptozotocin-induced diabetic rats were treated with 45 mg/kg lycopene + 1 U/day insulin for 30 days. The study assessed glycemia, insulin sensitivity, lipid profile and paraoxonase 1 (PON-1) activity in plasma. Superoxide dismutase (SOD) and catalase (CAT) activities and the protein levels of advanced glycation end-product receptor 1 (AGE-R1) and glyoxalase-1 (GLO-1) in the kidneys were also investigated. An effective glycemic control was achieved with lycopene plus insulin, which may be attributed to improvements in insulin sensitivity. The combined therapy decreased the dyslipidemia and increased the PON-1 activity. In the kidneys, lycopene plus insulin increased the activities of SOD and CAT and the levels of AGE-R1 and GLO-1, which may be contributing to the antialbuminuric effect. These findings demonstrate that lycopene may aggregate favorable effects to insulin against diabetic complications resulting from glycoxidative stress.

Effects of ethanolic extract of &lt;i&gt;Aristolochia repens&lt;/i&gt; on biochemical and histological changes in high-fat diet and streptozotocin-induced rats

The study evaluated the lipid profile, electrolytes and histological changes in diabetic Wistar rats treated with stem bark extract of Aristolochia repens. Type 2 diabetes was induced in rats with high-fat diet and low dose of streptozotocin (35 mg/kg body weight). A total of thirty-five Wistar rats were fed with high-fat diet for eight (8) weeks, while five (5) Wistar rats (Sham control) were fed with low-fat diet. Non-induced male Wistar rats were treated with distilled water (Sham control); while the induced male Wistar rats were treated with distilled water, metformin (100 mg/kg), 50, 100 and 200 mg/kg ethanolic extract of Aristolonchia repens stem bark for 28 days. The rats were sacrificed; liver, kidney and serum were collected and analyzed for serum glucose, lipid profile, electrolytes and histological changes. Treatment with ethanolic extract of Aristolonchia repens stem bark significantly reduced the body weight, glucose level, total cholesterol concentration, triglycerides, low-density lipoprotein concentration and atherogenic indices. Mild pathological alterations were observed in the liver and kidney of diabetic rats at dosage above 50 mg/kg. However, the extract reduced the blood glucose, lipids and improve the selected electrolyte balance. This study suggests that ethanolic extract of stem bark of A. repens possesses antihyperglycaemia and antilipidaemic potential and might not be safe at dosage above 50 mg/kg.

Phloretamide Protects against Diabetic Kidney Damage and Dysfunction in Diabetic Rats by Attenuating Hyperglycemia and Hyperlipidemia, Suppressing NF-κβ, and Upregulating Nrf2.

Potent hypoglycemic and antioxidant effects were recently reported for the apple-derived phenolic compound phloretamide (PLTM). The renoprotective effects of this compound are yet to be shown. This study aimed to examine the potential of PLTM to prevent diabetic nephropathy in streptozotocin-induced diabetic rats and to examine the possible mechanisms of protection. Non-diabetic and STZ-diabetic male rats were treated orally by gavage with either the vehicle or with PTLM (200 mg/kg; twice/week) for 12 weeks. PTLM significantly increased urine volume and prevented glomerular and tubular damage and vacuolization in STZ-diabetic rats. It also increased creatinine excretion and reduced urinary albumin levels and the renal levels of kidney injury molecule-1 (KIM-1), 8-hydroxy-2'-deoxyguanosine (8-OHdG), neutrophil gelatinase-associated lipocalin (NGAL), and nephrin in the diabetic rats. PTLM also prevented an increase in the nuclear levels of NF-κβ, as well as the total levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), caspase-3, and Bax in the kidneys of diabetic rats. These effects were associated with reduced serum levels of triglycerides, cholesterol, and low-density lipoprotein cholesterol. In both the control and diabetic rats, PTLM significantly reduced fasting plasma glucose and enhanced the renal mRNA and cytoplasmic levels of Nrf2, as well as the levels of Bcl2, superoxide dismutase (SOD), and glutathione (GSH). However, PTLM failed to alter the cytoplasmic levels of keap1 in diabetic rats. In conclusion, PTLM prevents renal damage and dysfunction in STZ-diabetic rats through its hypoglycemic and hypolipidemic activities, as well as through its antioxidant potential, which is mediated by activating the Nrf2/antioxidant axis.

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

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

The Protective Effects of Vanillic Acid and Vanillic Acid-Coated Silver Nanoparticles (AgNPs) in Streptozotocin-Induced Diabetic Rats.

The production of nanoparticles enhances the bioactivity of biological molecules for drug delivery to diseased sites. This study explains how silver nanoparticle (AgNP) coating enhanced the protection effects of vanillic acid in male diabetic rats with streptozotocin- (STZ-) induced diabetes. Twenty-four rats were divided into four groups (n = 6) for this investigation. The first group (G1) is untreated, whereas diabetes was induced in the other three groups through STZ injection. Diabetic rats that were not getting therapy were included in the second group (G2, STZ-positive), whereas the other diabetic rats were divided into the third group (G3, vanillic acid-treated) and the fourth group (G4, vanillic acid-coated AgNPs treated). The treatment lasted four weeks. In G2, the induction of diabetes significantly (at P = 0.05) increased in serum glucose, glycated proteins, renal indices, interleukin-6 (IL-6), K+, immunoglobulins, and lipid peroxidation, while decreased Ca++, Na+, and other antioxidants in the kidney tissue homogenate. In addition, pathological altered signs were present in the pancreas and kidneys of diabetic rats. The renal and pancreatic tissues were effectively enhanced by vanillic acid or vanillic acid-coated AgNPs, bringing them very close to their prediabetic conditions. Vanillic acid-coated AgNPs offered a stronger defense against STZ-induced diabetes and lessened the effects of hyperglycemia compared to ordinary vanillic acid. Additionally, using vanillic acid coated with silver nanoparticles greatly increased the antioxidant and antidiabetic activity and reduced inflammation when compared to using vanillic acid alone.

Effects of Berberis vulgaris fruit extract on oxidative stress status in the kidney and liver of diabetic rats.

Oxidative stress has a key role in the diabetes pathogenesis and complications. Berberis vulgaris is known in folk medicine for curing several diseases. The current research aimed to assess the influences of Berberis vulgaris fruit extract against oxidative stress in streptozotocin-induced diabetic rats. Streptozotocin (60 mg/kg, ip) was injected to male rats. After diabetes confirmation, animals received the Berberis vulgaris fruit extract daily at amounts of 3.5 and 7.5 % of drinking water (v/v) for six weeks. Total thiol and lipid peroxidation levels were assessed in the serum, liver, kidney and spleen at the end of the study. Diabetic rats exhibited hyperglycemia along with enhancement of lipid peroxidation levels in the serum, liver, kidney and spleen, and decrement of total thiol content in the kidney and liver tissues. Chronic administration of Berberis vulgaris fruit extract at amount of 3.5 % of drinking water decreased the lipid peroxidation level in the serum and liver, and enhanced total thiol level in the liver and kidney. Berberis vulgaris fruit extract exerts antioxidant activity in the serum, liver and kidney organs of diabetic rats. Therefore, it might be used in the prevention and control of diabetes complications.

Sirt1 activation prevents high glucose-induced angiotensin converting enzyme 2 downregulation in renal tubular cells by regulating the TIMP3/ADAM17 pathway.

Angiotensin converting enzyme 2 (ACE2) exerts renoprotective effects in diabetic kidney disease (DKD) by converting angiotensin (Ang) II into Ang(1-7). Previous studies have demonstrated that ACE2 expression in renal tubules is downregulated in DKD, but the mechanism is not fully understood. Sirtuin-1 (Sirt1) is a protein deacetylase that may regulate the activity of the renin-angiotensin system. The present study investigated the effects of Sirt1 on ACE2 expression under high glucose (HG) conditions and the underlying signaling pathway. Rats with DKD and NRK-52E cells cultured with HG were employed in this study. Western blotting, immunohistochemistry detection and qRT-PCR were performed for protein and mRNA expression analyses. Rats subjected to DKD displayed downregulated expression of Sirt1 and ACE2 in kidneys. Resveratrol, an activator of Sirt1, restored ACE2 expression and ameliorated renal injuries. Similarly, pharmacological activation of Sirt1 with SRT1720 markedly upregulated ACE2 in NRK-52E cells cultured with HG, while Sirt1 small interfering RNA (siRNA) further suppressed ACE2 expression. In addition, A disintegrin and metalloproteinase (ADAM) 17 was observed to be upregulated, and its inhibitor, tissue inhibitor of metalloproteinase 3 (TIMP3), was downregulated in the kidneys of diabetic rats and NRK-52E cells incubated with HG. The TIMP3/ADAM17 pathway was involved in the regulation of ACE2 expression, as evidenced by decreased ACE2 expression levels after TIMP3-siRNA pretreatment. SRT1720 ameliorated the imbalance of TIMP3/ADAM17 induced by HG and consequently enhanced the expression of ACE2. Notably, the above effect of SRT1720 on ACE2 was interrupted by TIMP3-siRNA. Our findings suggest that Sirt1 activation may prevent HG-induced downregulation of renal tubular ACE2 by modulating the TIMP3/ADAM17 pathway. Sirt1 stimulation might be a potential strategy for the treatment of DKD.

Evaluation of Phytochemical Composition, Proximate Analysis and Antioxidant Activity of Justicia Carnea Leaves on Streptozotocin – Induced Diabetic Wistar Rats

Introduction/Aim: Diabetes mellitus (DM) is a long-term metabolic condition characterized by consistently high blood sugar levels resulting from issues with insulin secretion, function, or both. This disorder, disrupts the normal breakdown and utilization of carbohydrates, lipids, and proteins, leading to a range of complications throughout the body. This study analyzed the proximate and phytochemical compositions of Justicia carnea leaves, a commonly used herbal plant in folk medicine and determined the antioxidant potential of the methanol extract of the leaves in streptozotocin (STZ)-induced diabetic wistar rats. Materials and Methods: Standard methods were employed to determine the proximate and phytochemical composition of the plant. For the antioxidant studies, a total of Thirty-six (36) male wistar rats weighing 180 to 200 g (mean weight = 190 ± 10 g) were divided into six (6) groups of six (6) rats each. Group 1 served as the normal control and received only water and grower’s pellet throughout, group 2 was induced with diabetes, but untreated, group 3 animals were induced with diabetes and treated with 50 mg/kg bw of metformin), groups 4, 5 and 6 were induced with diabetes and treated with 100, 200 and 500 mg/kg bw of methanol extract of Justicia carnea leaves respectively. Diabetes mellitus was induced in the rats by intraperitoneal injection of 50 mg/kg bw of STZ. After 21 days of the treatment, the animals were sacrificed and the pancreas, liver and kidney tissues were collected for biochemical analyses. Results: Phytochemical screening revealed the presence of flavonoids, tannins, steroids, phenols, and terpenoids, indicating significant bioactive potential. Proximate analysis showed high carbohydrate (47.88%) and moisture (22.12%) content, with lower levels of crude fat (0.23%) and protein (1.26%). A significant (p&lt;0.05) increase in the levels of fasting blood glucose and a significant (p&lt;0.05) decrease in enzymic antioxidants, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase in the pancreas, liver and kidney of diabetic rats were observed. Oral administration of methanol extract of Justicia carnea leaves, significantly (p&lt;0.05) decreased fasting blood glucose and improved the antioxidant status of diabetic rats in a dose dependent manner. Conclusion: This study highlights the significant proximate and phytochemical compositions of Justicia carnea leaves, revealing a high content of essential nutrients and bioactive compounds. The notable antioxidant activity observed, supports the plant’s use in traditional medicine and underscores its potential in the management of oxidative stress-induced diabetic complications.

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker on oxidative stress and metabolism of elements in kidney of STZ-induced diabetic rats

In diabetes, increased oxidative stress and impaired trace element metabolism play an important role in the pathogenesis of diabetic nephropathy. The objective of this research was to examine the outcomes of blocking the renin-angiotensin system, using either the angiotensin-converting enzyme inhibitor (ACEI), perindopril, or the angiotensin II type 1 (AT1) receptor blocker, irbesartan, on oxidative stress and trace element levels such as Zn, Mg, Cu, and Fe in the kidneys of diabetic rats that had been induced with streptozotocin.Thirty-two Wistar albino male rats were equally divided into four groups. The first group was used as a control. The second group of rats developed diabetes after receiving a single intraperitoneal dose of STZ. The third and fourth groups of rats had STZ-induced diabetes and received daily dosages of irbesartan (15 mg/kg b.w/day) and perindopril (6 mg/kg b.w/day) treatment, respectively.Biochemical analysis of the kidneys showed a distinct increase in oxidative stress, indicated by heightened levels of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activities, as well as reduced glutathione (GSH) levels in the kidneys of diabetic rats. In the kidneys of diabetic rats, the mean levels of Fe and Cu were found to be significantly higher than those of the control group. Additionally, the mean levels of Zn and Mg were significantly lower in the diabetic rats compared to the control rats. Both perindopril and irbesartan decreased significantly MDA content and increased SOD activities and GSH levels in the kidneys of rats with diabetes. The Zn and Mg concentrations in the kidneys of diabetic rats treated with perindopril and irbesartan were markedly higher than in untreated STZ-diabetic rats, while the Cu and Fe concentrations were significantly lower. The urinary excretion of rats treated with perindopril and irbesartan showed a pronounced increase in Cu levels, along with a significant reduction in Zn and Mg levels. Although diabetic rats demonstrated degenerative morphological alterations in their kidneys, both therapies also improved diabetes-induced histopathological modifications in the kidneys.Finally, the present results suggest that manipulating the levels of Zn, Mg, Cu, and Fe - either through ACE inhibition or by blocking AT1 receptors - could be advantageous in reducing lipid peroxidation and increasing antioxidant concentration in the kidneys of diabetic rats.

Plantain flour – A beneficial material for the organ and transcriptional profile of kidney of diabetic rats

This study investigated the ameliorative effects of plantain flour on the organs of diabetic rats, and explored the mechanism from the perspective of kidney transcription. Diabetes was induced in rats by streptozotocin (STZ) and a high-sugar and high-fat diet. The alleviation effects and molecular mechanism of diabetes by plantain flour at different doses (1 g/kg·Bw, 2 g/kg·Bw, and 4 g /kg·Bw) were evaluated based on the analysis of biochemical indicators, histological observations, homeostasis model, and kidney transcriptome. The findings demonstrated that the intervention of plantain flour can reduce the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and urea (UREA). The pathological study revealed that plantain flour can alleviate the pathological symptoms of fat accumulation in liver and kidney tissue. According to the homeostasis model, plantain flour was able to reduce insulin resistance in diabetic rats. Transcriptome analysis showed that plantain flour improved dyslipidemia by up-regulating Acsl1, down-regulating Fabp4 and Plin1, and reduced kidney injury by up-regulating Slco1a6, Hsd17b2, Cyp2c24, and Cyp2c11 genes. These results suggested that plantain flour could improve the organ damage caused by diabetes and has the potential to be developed into healthy food.

Gastroprotective evaluation of Medicago sativa L. (Fabaceae) on diabetic rats

Traditional uses for the plant Medicago sativa (M. sativa) (Alfalfa) (Family: Fabaceae) include liver protection, antioxidant activity, and the treatment of bleeding and digestive issues. This study aims to assess the effect of ethanol extract of M. sativa (EEMS) on experimental-induced ulcers in diabetic rats. By pylorus ligation and ethanol administration, gastric ulcers were induced in diabetic rats. Five groups each consisting of six rats in each model were used. All other groups except Group I were made diabetic by giving rats alloxan (140 mg/kg i.p.). Vehicles were given to Group I (normal control) and Group II (diabetes control) rats. Group III (positive control) received ranitidine 50 mg/kg, and Group IV and V received EEMS at doses of 100 and 400 mg/kg, respectively. In the pylorus ligation and ethanol-induced stomach ulcer model of rats, the findings demonstrated that EEMS (100 mg/kg) showed a decreased ulcer index of 2.01 ± 0.41 and was found statistically significant against the diabetes control group (p < 0.001) as well as, an ulcer index of 0.68 ± 0.22 by EEMS (400 mg/kg) with a significant reduction in the ulcer index (p < 0.001). EEMS (100 and 400 mg/kg) reduce free acidity by 13.16 ± 0.65 mEq/L and 9.83 ± 0.30 mEq/L, respectively. EEMS also showed a protective impact on the liver and kidneys of diabetic rats. Antihyperglycemic action was also discovered in diabetic animals. The findings of the current investigation demonstrated that ethanolic extract of M. sativa possesses anti-ulcer activity in diabetic rats. Ethanolic extract of M. sativa may be a treatment option for stomach ulcers that also have diabetes.