Streptozotocin-induced Diabetic Rats Research Articles

Therapeutic potential of bark extracts from Macaranga denticulata on renal fibrosis in streptozotocin-induced diabetic rats

ABSTRACT Macaranga denticulata (MD) bark is commonly utilized in traditional medicine for diabetes prevention and treatment. The bark extract of MD is rich in prenyl or farnesyl flavonoids and stilbenes, which possess antioxidant properties. Although data suggest the potential therapeutic benefits of the use of MD in treating diabetic nephropathy (DN), the precise mechanisms underlying MD-initiated protective effects against DN are not well understood. This study aimed to assess the renoprotective properties of MD extract by examining renofibrosis inhibition, oxidative stress, and inflammation utilizing streptozotocin-induced DN male Sprague – Dawley rats. Diabetic rats were intraperitoneally injected with streptozotocin (STZ) to induce diabetes. After 6 days, these rats were orally administered MD extract (200 mg/kg/day) or metformin (200 mg/kg/day) for 14 days. The administration of MD extract significantly lowered blood glucose levels, restored body weight, and reduced urine levels of various biomarkers associated with kidney functions. Histopathological analysis revealed protective effects in both kidneys and pancreas. Further, MD extract significantly restored abnormalities in advanced glycation end products, oxidative stress biomarkers, and proinflammatory cytokine levels in STZ-treated rats. MD extract markedly reduced renal fibrosis biomarker levels, indicating recovery from renal injury, and reversed dysregulation of sirtuins and claudin-1 in the kidneys of rats with STZ-induced diabetes. In conclusion, data demonstrated the renoprotective role of MD extract, indicating plant extract’s ability to suppress oxidative stress and regulate proinflammatory pathways during pathological changes in diabetic nephropathy.

Neuroprotective effect of Lannea egregia Alkaloid-rich leaf extracts in streptozotocin-induced diabetic rats

BackgroundStudies suggest that medicinal plant extracts can help reduce the neuron degeneration associated with diabetes. In this study, the neuroprotective effect of the alkaloid-rich extract from the leaves of Lannea egregia was assessed in rats with diabetes induced by streptozotocin (STZ). MethodsLannea egregia alkaloid-rich analysis was carried out via a known procedure. The rats were randomly assigned into five treatment groups (n = 8): normal control, diabetic-induced rats (45 mg/kg STZ), and diabetic rats treated with low doses of Lannea egregia leaf alkaloid-rich extract (50 mg/kg b.w, LEL) and high (100 mg/kg b.w, LEH) (300 mg/kg and 150 mg/kg), and metformin (200 mg/kg). On 22nd day of the experiment, animals were sacrificed, and their blood and brains were collected for neuro-biomarker analysis. ResultsDiabetic-induced rats that received metformin, LEL and LEH exhibited considerably reduced levels of dopamine, serotonin, norepinephrine, NO, MDA, and AChE, BChE activities when compared to untreated diabetic animals. Additionally, rats with diabetes that received treatment with metformin, LEL and LEH displayed a noticeable increase in ENTPDase, Na/K ATPase, GST, CAT, GPx, and SOD activities when compared to the untreated diabetic rats. Histological examination revealed improved brain architecture in the treated groups in contrast to those in diabetic-induced rats. ConclusionThe alkaloid-rich extracts of Lannea egregia might be effective in normalizing brain damage caused by complications of diabetes mellitus.

Therapeutic potential of aquatic Stevia extract in alleviating endoplasmic reticulum stress and liver damage in streptozotocin-induced diabetic rats.

Misfolded proteins accumulate in the liver due to endoplasmic reticulum stress (ERS) caused by high blood glucose levels in diabetes. This triggers the unfolded protein response (UPR), which if persistently activated, results in cellular dysfunction. Chronic ER stress increases inflammation, insulin resistance, and apoptosis. There is growing interest in using native plants and traditional medicine for diabetes treatment. The stevia plant has recently gained attention for its potential therapeutic effects. This study investigates the protective effects of aquatic stevia extract on liver damage, ER stress, and the UPR pathway in streptozotocin (STZ)-induced diabetic rats. Rats were randomly divided into four groups: a control group that received 1ml of water; a diabetic group induced by intraperitoneal injection of STZ (60mg/kg); a diabetic group treated with metformin (500mg/kg); and a diabetic group treated with aquatic extracts of stevia (400mg/kg). After 28 days, various parameters were assessed, including inflammatory markers, oxidative stress indices, antioxidant levels, gene expression, stereology, and liver tissue pathology. Compared to the diabetic control group, treatment with stevia significantly decreased serum glucose, liver enzymes, inflammatory markers, and oxidative stress while increasing body weight and antioxidant levels. Additionally, stevia extract manipulated UPR gene expression and reduced apoptosis pathway activation. Histological examination revealed improved liver tissue morphology in stevia-treated diabetic rats. These findings suggest that aquatic stevia extract mitigates ER stress in diabetic rats by modulating the IRE-1 arm of the UPR and apoptosis pathways, highlighting its potential therapeutic benefits for diabetes-related liver complications.

L-Arginine-Loaded Oxidized Isabgol/Chitosan-Based Biomimetic Composite Scaffold Accelerates Collagen Synthesis, Vascularization, and Re-epithelialization during Wound Healing in Diabetic Rats.

Impaired wound healing in diabetic wounds is common due to infection, inflammation, less collagen synthesis, and vascularization. Diabetic wound healing in patients is still a challenge and needs an ideal wound dressing to treat and manage diabetic wounds. Herein, an efficacious wound dressing biomaterial was fabricated by cross-linking oxidized isabgol (Oisab) and chitosan (Cs) via trisodium trimetaphosphate and Schiff base bonds. l-Arginine (l-Arg) was incorporated as a bioactive substance in the Oisab + Cs scaffold to promote cell adhesion, cell proliferation, collagen synthesis, and vascularization. The fabricated scaffolds showed microporous networks in the scanning electron microscopy analysis. The scaffold also possessed excellent hemocompatibility. In vitro studies using fibroblasts (L929 and human dermal fibroblast cells) confirmed the cytocompatibility of these scaffolds. The results of the in vivo chicken chorioallantoic membrane assay confirmed the proangiogenic activity of the Oisab + Cs + l-Arg scaffolds. The wound-healing potential of these scaffolds was studied in streptozotocin-induced diabetic rats. This in vivo study showed that the period of epithelialization in the Oisab + Cs + l-Arg scaffold-treated wounds was 21.67 ± 1.6 days, which was significantly faster than the control (30.33 ± 2.5 days). Histological and immunohistochemical studies showed that the Oisab + Cs + l-Arg scaffolds significantly accelerated the rate of wound contraction by reducing inflammation, improving collagen synthesis, and promoting neovascularization. These findings suggest that the Oisab + Cs + l-Arg scaffolds could be beneficial in treating diabetic wounds in clinical applications.

Rosemary leaf extract alleviates testicular impairment, oxidative stress, and apoptosis in streptozotocin-induced diabetic rats

Rosemary leaf extract alleviates testicular impairment, oxidative stress, and apoptosis in streptozotocin-induced diabetic rats

Assessment of organ weight changes in normal and streptozotocin-induced diabetic rats treated with <i>Olea europaea L.</i> leaf extract

Assessment of organ weight changes in normal and streptozotocin-induced diabetic rats treated with <i>Olea europaea L.</i> leaf extract

Molecular hybridization, synthesis, in vitro α-glucosidase inhibition, in vivo antidiabetic activity and computational studies of isatin based compounds

In the pursuit of novel antidiabetic agents, a series of isatin-thiazole derivatives (7a-7j) were synthesized and characterized using a range of spectroscopic techniques. The enzyme inhibitory activities of the target analogues were assessed using both in vitro and in vivo assays. The tested compounds 7a-7j demonstrated In vitro inhibitory potential against α-glucosidase, as indicated by their IC50 values ranging from 28.47 to 46.61 µg/ml as compared to standard drug acarbose IC50 value of 27.22 ± 2.30 µg/ml. Additionally, compounds 7d and 7i were chosen for in vivo evaluation of their antidiabetic efficacy in streptozotocin-induced diabetic Wistar rats. These compounds exhibited significant antidiabetic activity both in vitro and in vivo, compound 7d produces therapeutic effects compared to standard pioglitazone by decreasing glycaemia and triglyceride levels in diabetic animals. Furthermore, a molecular docking study was conducted to elucidate the binding interactions of the compounds within the α-glucosidase enzyme binding pocket (PDB ID 3A47) and stability was confirmed by dynamics simulation trajectories. Thus, from the above findings, it may demonstrate that isatin-thiazole hybrids constitute promising candidates in the pursuit of developing newer oral antidiabetic agents.

Bioinspired Collagen Scaffold Loaded with bFGF-Overexpressing Human Mesenchymal Stromal Cells Accelerating Diabetic Skin Wound Healing via HIF-1 Signal Pathway Regulated Neovascularization.

The healing of severe chronic skin wounds in chronic diabetic patients is still a huge clinical challenge due to complex regeneration processes and control signals. Therefore, a single approach is difficult in obtaining satisfactory therapeutic efficacy for severe diabetic skin wounds. In this study, we adopted a composite strategy for diabetic skin wound healing. First, we fabricated a collagen-based biomimetic skin scaffold. The human basic fibroblast growth factor (bFGF) gene was electrically transduced into human umbilical cord mesenchymal stromal cells (UC-MSCs), and the stable bFGF-overexpressing UC-MSCs (bFGF-MSCs) clones were screened out. Then, an inspired collagen scaffold loaded with bFGF-MSCs was applied to treat full-thickness skin incision wounds in a streptozotocin-induced diabetic rat model. The mechanism of skin damage repair in diabetes mellitus was investigated using RNA-Seq and Western blot assays. The bioinspired collagen scaffold demonstrated good biocompatibility for skin-regeneration-associated cells such as human fibroblast (HFs) and endothelial cells (ECs). The bioinspired collagen scaffold loaded with bFGF-MSCs accelerated the diabetic full-thickness incision wound healing including cell proliferation enhancement, collagen deposition, and re-epithelialization, compared with other treatments. We also showed that the inspired skin scaffold could enhance the in vitro tube formation of ECs and the early angiogenesis process of the wound tissue in vivo. Further findings revealed enhanced angiogenic potential in ECs stimulated by bFGF-MSCs, evidenced by increased AKT phosphorylation and elevated HIF-1α and HIF-1β levels, indicating the activation of HIF-1 pathways in diabetic wound healing. Based on the superior biocompatibility and bioactivity, the novel bioinspired skin healing materials composed of the collagen scaffold and bFGF-MSCs will be promising for healing diabetic skin wounds and even other refractory tissue regenerations. The bioinspired collagen scaffold loaded with bFGF-MSCs could accelerate diabetic wound healing via neovascularization by activating HIF-1 pathways.

Chrysin attenuates hyperglycemia associated with hepatorenal and glycoprotein abnormalities via regulation of glucose metabolism in HFD/STZ- induced diabetic rats

BackgroundFlavonoids like chyrsin, which are abundant in plant extracts, honey, and bee propolis, have antiviral, anti-cancer, anti-bacterial, anti-inflammatory, anti-allergic, anti-mutagenic, anti-anxiolytic, and other therapeutic uses. However, no research has been published on how chrysin protects rats against HFD/STZ- induced changes to the glycoprotein moiety via controlling the metabolism of glucose. MethodsFor two weeks, albino male wistar rats were fed a high-fat diet in order to develop diabetes. Upon two weeks, a low dosage of streptozotocin (35 mg/kg, diluted in 0.1 M sodium citrate buffer, pH 4.5) was administered into the animals after they had been fasted for the whole night. Blood glucose, insulin, hepatic, and renal indicators were analyzed using commercially available diagnostic kits, and other parameters were ascertained biochemically. ResultsFor 30 days, high-fat diet- and streptozotocin-induced diabetic rats were given 40 mg/kg b.w./day of chrysin, which significantly reduced blood glucose, homeostatic model assessment of insulin resistance, glycogen phospharylase, hepatic and renal markers, and increased insulin, glycogen content, and glycogen synthase levels. ConclusionHowever, the altered activity of the glycoprotein components and the carbohydrate metabolic enzymes was restored upon chrysin administration. On several criteria, the chrysin's effect was similar to that of metformin. Chrysin is therefore a potential antidiabetic agent.

Potential Effect of Curcumin in Lowering Blood Glucose Level in Streptozotocin-Induced Diabetic Rats.

The prevalence of diabetes mellitus has significantly increased, with 537 million individuals living with diabetes in 2021. Curcumin, a natural compound present in turmeric, has anti-inflammatory and antioxidant properties that aid in controlling diabetes. Curcumin can lower blood glucose levels, increase pancreatic cell function, and reduce insulin resistance. The pathophysiology of diabetes involves oxidative stress and endoplasmic reticulum stress, which can lead to cell death. This study aimed to evaluate the antidiabetic activity of curcumin in rats by administering it for a month and evaluating pancreatic tissue histology. STZ-induced diabetic rats were fed a high-fat diet containing glibenclamide, 200 mg/kg body weight (BW) curcumin, 400 mg/kg BW curcumin, or a placebo for 4 weeks. After intervention, blood glucose levels were measured, and the pancreatic tissue was examined. Blood glucose levels were measured at 0, 2, 4, 6, and 8 h. One-way ANOVA was performed to measure the mean difference among the groups at 0, 2, 4, 6, and 8 h of observation, which reported a statistically significant difference (p < 0.05). The blood glucose levels decreased after 4 h in the group receiving curcumin. Histological evaluation of the pancreas showed slight hydropic degeneration after 4 weeks of curcumin treatment. Our study indicates that curcumin has a beneficial effect in diabetic rats by reducing blood glucose levels and a protective effect on the pancreas.

Hypoglycemic effects of organic extracts from Ganoderma sp. and Kombucha in streptozotocin-induced diabetic Wistar rats

Evaluate the hypoglycemic effects of Kombucha and Ganoderma aqueous extractsin a model of diabetes with streptozotocin. Eight-week-ol male wistar ratsweighimg approximately 180 g were randomized into four groups (12 rats eachgroup). Control group (C), streptozotocin (E) without treatment, Kombucha (K)was given Kombucha extract 324 mg/kg orally, and Ganoderma group (G) wasgiven 250 mg/kg orally both for 45 days. Four animals per group were sacrificedat 2-, 15- and 45-days post treatment. Consumption of water and food wereregistered. Blood glucose and insulin levels were measured by spectrophotometryand the islets of Langerhans in the pancreas were quantified by ELISA assay. Datawere analyzed with an ANOVA two-ways and Tukey’s test as post hoc, Sigmastat3.1 Software was used and 0.05% significance was considered. Among the mainresults found, both extracts presented hypoglycemic effects after 15 days oftreatment. An interaction between the number of islets, insulin synthesis, water,and food consumption were also found with the streptozotocin group thatpresented the lowest average number of islets compared to other groups. Bothextracts showed a hypoglycemic, protective and regenerative effect on thepancreas, with differences observed in the physical condition of the animalstreated with Ganoderma, which showed signs of cachexia.

Tocotrienol-rich fraction (TRF) protects against retinal cell apoptosis and preserves visual behavior in rats with streptozotocin-induced diabetic retinopathy

BackgroundTocotrienol is a vitamin E analogue that is known to exert anti-inflammatory and antioxidant effects. Hence, in the current study, the effects of TRF on the expression of pro- and anti-apoptotic proteins in the streptozotocin-induced diabetic rat retinas were investigated. The effect of TRF on the visual behaviour of rats was also studied.MethodsDiabetes was induced in rats by intraperitoneal injection of streptozotocin and was confirmed by a blood sugar level of at least 20 mmol/L, 48 h, post-injection. Diabetic rats were divided into a group treated with vehicle (DV) and the other treated with TRF (100 mg/kg; DT). A group of non-diabetic rats treated with vehicle (N) served as the control group. All treatments were administered orally for 12 weeks. Rats were then subjected to an assessment of general behaviour in an open field arena and a two-chamber mirror test to assess their visual behaviour. At the end of the experimental period, rats were sacrificed, and their retinas were isolated to measure the expression of pro- (Casp3, Bax) and anti-apoptotic (Bcl2) markers using RT-qPCR and ELISA. TUNEL staining was used to detect the apoptotic retinal cells.ResultsTreatment with TRF lowered the retinal expression of Casp3 protein by 2.26-folds (p < 0.001) and Bax protein by 2.18-fold (p < 0.001) compared to vehicle-treated rats. The retinal anti-apoptotic protein Bcl2 expression was 1.87-fold higher in DT compared to DV rats (p < 0.001). Accordingly, the Bax/Bcl2 ratio in the TRF-treated group was significantly greater in DT compared to DV rats. Retinal Casp3, Bax, and Bcl2 gene expression, as determined by RT-qPCR, also showed changes corresponding to protein expression. In the open field test, DV rats showed greater anxiety-related behaviour than group N, while the behaviour of DT rats was similar to the N group of rats. DT rats and group N rats preferred the inverse mirror chamber over the mirror-containing chamber in the two-mirror chamber test (p < 0.01).ConclusionOral TRF therapy for 12 weeks lowers retinal cell apoptosis by decreasing pro- and increasing anti-apoptotic markers. The preservation of visual behaviour in a two-chamber mirror test supported these retinal molecular alterations in diabetic rats.

Metformin as a Modulator of Autophagy and Hypoxia Responses in the Enhancement of Wound Healing in Diabetic Rats.

The molecular mechanisms underlying delayed wound repair in diabetes involve dysregulation of key cellular processes, including autophagy and hypoxia response pathways. Herein, we investigated the role of topical metformin, an established anti-diabetic drug with potential autophagy-inducing properties, in improving wound healing outcomes under hypoxic conditions. Full-thickness skin wounds were created in streptozotocin-induced diabetic rats, and tissue samples were collected at regular intervals for molecular and histological analysis. The expression levels of autophagy markers LC3B and Beclin-1 were evaluated via immunohistochemistry and qRT-PCR, while the amount of AMP-activated protein kinase (AMPK) and hypoxia-inducible factor-1α (HIF-1α) were determined via ELISA. Our results demonstrated that metformin administration resulted in the upregulation of LC3B and Beclin-1 in the wound bed, suggesting induction of autophagy in response to the treatment. Mechanistically, metformin treatment also led to the increased amount of AMPK, a critical regulator of cellular energy homeostasis, and a subsequent reduction in HIF-1α amount under hypoxic conditions. In conclusion, our findings demonstrate that metformin promotes wound healing in diabetes mellitus by enhancing autophagy through AMPK activation and modulating HIF-1α amount in a hypoxic microenvironment. This study offers a new therapeutic approach by shedding light on the potential benefits of metformin as adjunctive therapy in diabetic wound management.

Anti-diabetic Effect of Quercetin-loaded Solid Lipid Nanoparticles in Streptozotocin-induced male Diabetic Rats

Anti-diabetic Effect of Quercetin-loaded Solid Lipid Nanoparticles in Streptozotocin-induced male Diabetic Rats

Antidiabetic effects of aqueous leaf extract of Vernonia amygdalina on serum liver markers in streptozotocin-induced diabetic albino Rats: a new data to support its Anti-diabetic effect

BackgroundNumerous plants have been explored for their potential antidiabetic properties, and Vernonia amygdalina (VA) stands among them. This study aims to investigate the antidiabetic activities of VA and validate its efficacy.MethodsAn aqueous extract of Vernonia amygdalina leaves was obtained through maceration. The antidiabetic effects of this plant extract were evaluated in vivo using diabetic model rats. Albino Wistar rats were induced into a diabetic state through intraperitoneal injection of streptozocin and subsequently treated with an optimal dose of 250 mg/kg aqueous extract of VA over a 21-day period. Parameters such as body weight, blood glucose levels, and serum marker enzymes were measured.ResultsThe results demonstrated a significant reduction (p < 0.05) in the glucose levels of streptozocin-induced diabetic rats following treatment with VA extract, highlighting its potential as an antidiabetic agent that performed comparably to the reference drug, glimepiride. Additionally, a significant increase (p < 0.05) in the body weight of the treated diabetic rats was observed. Aqueous extracts also significantly (p < 0.05) altered the serum concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in a manner similar to the glimepiride-treated group.ConclusionThis study affirms the anti-diabetic effects of the aqueous extract of Vernonia amygdalina in streptozotocin-induced diabetic rats and suggests that the extract holds promise as an important phytomedicine for the development of more effective treatments for diabetes.

Retraction Note: Ameliorative potential of Operculina turpethum against streptozotocin-induced diabetes in rats: biochemical and histopathological studies.

[This retracts the article DOI: 10.1007/s13205-021-02811-x.].

Microencapsulated sardine Oil using vanillic acid grafted chitosan as wall material: Alleviating effect on streptozotocin-induced hyperglycemia in rats

Impact of an innovative antioxidant wall material, vanillic acid-grafted chitosan, on enhancement of oxidative stability was investigated. Microencapsulation with the aid of spray drying was proven to be an effective method for preserving omega-3 fatty acids. Streptozotocin-induced diabetic rats were used to examine the effects of microcapsules loaded with sardine oil and vanillic acid-grafted chitosan (SO-MC) as wall material. Antioxidant and anti-hyperglycemic effects were significantly enhanced in rat models treated with 500 mg/kg of SO-MC. The lack of aberrant weight fluctuations or mortality in an acute toxicity assessment indicated that there were no symptoms of toxicity. Addition of SO-MC into the meal resulted in dose-dependent decreases in blood glucose levels as compared to the diabetes control group. Treatment with SO-MC reduced lipid peroxidation, whereas increased production of glutathione peroxidase (GPx) and glutathione S-transferase (GSH), two crucial antioxidants, as compared to the diabetes control group. These findings underscore the potential utility of SO-MC as a promising dietary supplement for the management of hyperglycemia

Effect of Dalbergiella welwitschi alkaloid-rich extracts on neuroprotective in streptozotocin-induced diabetic rats.

The neuroprotective ability of alkaloid-rich leaf extract of Dalbergiella welwitschii in streptozotocin-induced type 2 diabetic rats were investigated in this study. Dalbergiella welwitshii leaf alkaloid-rich extract was obtained using standard procedure. Streptozotocin was injected into the experimental animals intraperitoneally at a dose of 45mg/mg body weight. Prior to this, the animals were given 20% (w/v) fructose for one week. The animals were grouped into five (n = 8), comprising of normal control (NC), diabetic control (DC), diabetic rats treated with low (50mg/mg body weight) and high (100mg/kg body weight) doses of Dalbergiella welwitschii alkaloid-rich leaf extracts (i.e., DWL and DWH respectively) and 200mg/kg body weight of metformin (MET). The animals were sacrificed on the 21st day, blood and brain tissue were harvested and used for the determination of neurotransmitters, cholinesterase, some ATP activities, oxidative stress biomarkers and histological examination. The results show that diabetic rats placed on DWL, DWH and MET significantly (p < 0.05) reduced cholinergic, elevated some ATPase activities and ameliorated oxidative stress biomarkers. These were supported by the histological examination by improving neuroprotective effects in diabetic rats administered DWL, DWH and MET. Hence, it can be presumed that DWL and DWH could be beneficial in treating diabetic neurodegenerative diseases.

Relationship Between Oxidative Stress in the Rotator Cuff and Transcutaneous Advanced Glycation End-Products Measurement in Diabetic Rats.

Diabetes mellitus increases oxidative stress due to hyperglycemia, resulting in the degeneration of rotator cuff tissue. Currently, there is no established method to non-invasively assess the extent of this oxidative stress. To address this, we aimed to investigate the relationship between the accumulation of advanced glycation end-products (AGEs), a marker of oxidative stress, and transcutaneous autofluorescence intensity in rotator cuff tissue harvested from diabetic rats. Ten control Sprague-Dawley (SD) rats and streptozotocin-induced diabetic rats (n = 10 per group) were used. The rats were euthanized eight and 16 weeks after the induction of diabetes, and rotator cuff attachment sites were collected and histologically analyzed. Prior to euthanasia, autofluorescence intensity was measured transcutaneously in the rotator cuff area. The expressions of AGEs and type I collagen were evaluated immunohistochemically with specific antibodies and the stained areas were quantified. All data were statistically analyzed using the Mann-Whitney U test. Correlation analysis was performed for skin autofluorescence intensity and the percentage of AGEs staining area using Spearman's rank correlation coefficient. The immunohistochemical expression of AGEs at the rotator cuff attachment sites and transcutaneous AGEs measurements were significantly higher in diabetic rats than in the control group at 16 weeks. There was no significant difference in the level of type 1 collagen between the two groups. This study reveals that the accumulation of AGEs in rotator cuff tissue increases due to prolonged hyperglycemia in diabetes. In addition, transcutaneous skin fluorescence intensity may be related to histological oxidative stress at the rotator cuff.

Intestinal Absorption and Transformation of the Increased Dose of Paracetamol in Streptozotocin-Induced Diabetic Rats

Intestinal Absorption and Transformation of the Increased Dose of Paracetamol in Streptozotocin-Induced Diabetic Rats