Hyperglycemia-induced oxidative stress in diabetic complications

Reactive oxygen species are increased by hyperglycemia. Hyperglycemia, which occurs during diabetes (both type 1 and type 2) and, to a lesser extent, during insulin resistance, causes oxidative stress. Free fatty acids, which may be elevated during inadequate glycemic control, may also be contributory. In this review, we will discuss the role of oxidative stress in diabetic complications. Oxidative stress may be important in diabetes, not just because of its role in the development of complications, but because persistent hyperglycemia, secondary to insulin resistance, may induce oxidative stress and contribute to beta cell destruction in type 2 diabetes. The focus of this review will be on the role of oxidative stress in the etiology of diabetic complications.     

On the potential increase of the oxidative stress status in patients with abdominal aortic aneurysm

Abstract

Background

Abdominal aortic aneurysm (AAA) is a major cause of preventable deaths in older patients. Oxidative stress has been suggested to play a key role in the pathogenesis of AAA. However, only few studies have been conducted to evaluate the blood oxidative stress status of AAA patients.

Methods and results

Twenty seven AAA patients (mean age of 70 years) divided into two groups according to AAA size (≤50 or >50 mm) were compared with an age-matched group of 18 healthy subjects. Antioxidants (vitamins C and E, β-carotene, glutathione, thiols, and ubiquinone), trace elements (selenium, copper, zinc, and copper/zinc ratio) and markers of oxidative damage to lipids (lipid peroxides, antibodies against oxidized patients, and isoprostanes) were measured in each subject. The comparison of the three groups by ordinal logistic regression showed a significant decrease of the plasma levels of vitamin C (P = 0.011), α-tocopherol (P = 0.016) but not when corrected for cholesterol values, β-carotene (P = 0.0096), ubiquinone (P = 0.014), zinc (P = 0.0035), and of selenium (P = 0.0038), as AAA size increased. By contrast, specific markers of lipid peroxidation such as the Cu/Zn ratio (P = 0.046) and to a lesser extent isoprostanes (P = 0.052) increased.

Conclusion

The present study emphasizes the potential role of the oxidative stress in AAA disease and suggests that an antioxidant therapy could be of interest to delay AAA progression.     

Oxidative stress and antioxidant status in patients with autoimmune liver diseases

Abstract

Objective

To estimate oxidative stress and antioxidant components during different stages of autoimmune liver diseases and assess their possible implication on disease progression.

Methods

We determined several markers of oxidative injury (isoprostane, aldehydes, protein carbonyls, 3-nitrotyrosine, and myeloperoxidase) and antioxidant components (glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase) in whole blood, serum, and urine in 49 patients with autoimmune cholestatic liver diseases (AC) and 36 patients with autoimmune hepatitis (AIH) and healthy subjects matched for sex and age.

Results

Both AC and AIH patients had increased levels of all lipid and protein oxidative injury products and significantly decreased whole blood glutathione levels compared to controls. AIH patients had significantly higher levels of aldehydes and glutathione peroxidase activity and significantly lower protein carbonyl levels compared to AC patients. Protein carbonyl and isoprostane levels increased and glutathione levels decreased gradually with progression from mild fibrosis to severe fibrosis and cirrhosis in both AC and AIH patients. In addition, both cirrhotic AC and AIH patients had significantly higher protein carbonyls compared to non-cirrhotics.

Discussion

We provide novel findings in support of a major contribution of oxidant/antioxidant imbalance in the progression of liver injury in AC and AIH.     

Serum and urine malondialdehyde levels in NIDDM patients with and without hyperlipidemia

Malondialdehyde (MDA), a marker of lipid peroxidation, was measured as thiobarbituric acid reactive substance (TBARS) in 78 noninsulin-dependent diabetic patients, 38 hyperlipidemic patients, and 28 healthy subjects. Diabetic patients were divided into groups and subgroups according to the existence of hyperlipidemia and other complications. Serum and urine MDA concentrations were significantly higher in diabetic and nondiabetic patient groups than in the control group. By contrast to urine MDA level, serum MDA level was significantly higher in hyperlipidemic diabetics than that of normolipidemic diabetics. Serum MDA levels in the hyperlipidemic diabetic group and urine MDA levels in both diabetic groups were significantly higher than those in hyperlipidemic nondiabetic group. In both diabetic groups, the existence of complications didn't affect serum and urine MDA levels. No correlation existed between serum and urine MDA levels in both patient groups and control subjects. This study confirmed the existence of lipid peroxidation disorders in diabetic patients.     

Antihyperglycemic effect of a new thiazolidinedione analogue and its role in ameliorating oxidative stress in alloxan-induced diabetic rats

Thiazolidinediones (TZDs) are a new class of antidiabetic drugs, having an insulin sensitizing effect in patients with type 2 diabetes. The contribution of oxidative stress from the standpoint of lipid and protein damage, alteration in endogenous antioxidant enzymes and effects of newly synthesized compounds, 5-[4-2-(6,7-Dimethyl-1,2,3,4-tetrahydro-2-oxo-4-quinoxalinyl)ethoxy]phenyl]methylene]thiazolid- ine-2,4-dione, (C(1)) in normal/alloxan-induced diabetic rats form the focus area of this study. Its effect was compared to two well-known TZDs, namely pioglitazone and rosiglitazone. It has been concluded from results that after thirty days of administration of C(1), Pg and Rg in alloxan-induced diabetic animal groups, the blood glucose level decreased, more remarkably in C(1) treated group. Also oxidative damage has been studied by estimating hepatic superoxide dismutase (SOD) activity, which was found to be increased (p<0.001 vs. control). An inverse change in SOD values between hepatic and pancreatic/kidney tissues were observed. Treatment with the test compounds lowered the activity of SOD in liver while increased its activity in kidney and pancreas. Similar normalizing effect of C(1) on liver, pancreatic and renal catalase (CAT)/ glutathione peroxidase (GPx) activities were pronounced in diabetic rats (p<0.001 vs. diabetic rats). Decreased reduced glutathione (GSH) content, found in diabetic animals, was significantly elevated to normal levels by C(1) treatment. The treatment with C(1) also decreased the levels of nitric oxide and increased the activities of glutathione-s-transferase and glutathione reductase, as compared to diabetic animals. Evidence of oxidative damage to lipids and proteins was shown through the quantification of protein carbonyl (in tissues) and malondialdehyde levels (both serum and tissues). It was observed that the protein/lipid damage in diabetic rats was improved by treatment with C(1). Total antioxidant activity (TAA) was found to be enhanced in C(1) treated rats (p>0.05 vs. group3, p<0.001 vs. group2, p<0.001 vs. group 4). These results suggest that the newly synthesized TZD derivative (C(1)) has a potential to act as antihyperglycemic and antioxidant agent. In addition, for all parameters checked, it has better efficacy than rosiglitazone and is as effective as pioglitazone.     

Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease

Alzheimer disease (AD) is a neurodegenerative disease which is characterized by the presence of extracellular senile plaques mainly composed of amyloid-beta peptide (Abeta), intracellular neurofibrillary tangles, and selective synaptic and neuronal loss. AD brains revealed elevated levels of oxidative stress markers which have been implicated in Abeta-induced toxicity. In the present work we addressed the hypothesis that oxidative stress occurs early in the development of AD and evaluated the extension of the oxidative stress and the levels of antioxidants in an in vivo model of AD, the triple-transgenic mouse, which develops plaques, tangles, and cognitive impairments and thus mimics AD progression in humans. We have shown that in this model, levels of antioxidants, namely, reduced glutathione and vitamin E, are decreased and the extent of lipid peroxidation is increased. We have also observed increased activity of the antioxidant enzymes glutathione peroxidase and superoxide dismutase. These alterations are evident during the Abeta oligomerization period, before the appearance of Abeta plaques and neurofibrillary tangles, supporting the view that oxidative stress occurs early in the development of the disease.     

Longevity and antioxidant enzymes,non-enzymatic antioxidants and oxidative stress in the vertebrate lung: a comparative study

It has been proposed that antioxidants can be longevity determinants in animals. However, no comprehensive study has been conducted to try to relate free radicals with maximum life span. This study compares the lung tissue of various vertebrate species — amphibia, mammals and birds — showing very different and well known maximum life spans and life energy potentials. The lung antioxidant enzymes superoxide dismutase, catalase, Se-dependent and non-Se-dependent glutathione peroxidases, and glutathione reductase showed significantly negative correlations with maximum life span. The same was observed for the lung antioxidants, reduced glutathione and ascorbate. It is concluded that a generalized decrease in tissue antioxidant capacity is a characteristic of longevous species. It is suggested that a low rate of free radical recycling (free-radical generation and scavenging) can be an important factor involved in the evolution of high maximum animal longevities. A low free-radical production could be responsible for a low rate of damage at critical sites such as mitochondrial DNA.Abbreviations CAT catalase - COX cytochrome oxidase - GPx glutathione peroxidase - GR glutathione reductase - GSH reduced glutathione - GSSG oxidized glutathione - LEP life energy potential - MDA malondialdehyde - MLSP maximum life span - MR metabolic rate - MW molecular weight - PO₂ partial pressure of oxygen - SOD superoxide dismutase - VO₂ basal oxygen consumption     

Markers for oxidative stress associated with soft rots in French beans (Phaseolus vulgaris) infected by Botrytis cinerea

The role of active oxygen species has been studied in spreading soft-rot lesions caused by the necrotrophic fungal pathogen Botrytis cinerea Pers.:Fr. in leaves of four genotypes of French bean (Phaseolus vulgaris L.). Large increases were observed for the aldehydic end-products of oxidative damage, malondialdehyde and 4-hydroxy-2-nonenal, as a result of infection in each of the genotypes studied. Similar increases were found in a stable free radical and g=4.27 Fe(III) signals, but not Mn(II) signals, in electron paramagnetic resonance spectra. These changes were accompanied by large decreases in ascorbic acid levels, with changes in the antioxidant glutathione being genotype dependent. Received: 3 May 2000 / Accepted: 13 July 2000     

The role of oxidative stress in diabetic complications

The morbidity and mortality associated with diabetes is the result of the myriad complications related to the disease. One of the most explored hypotheses to explain the onset of complications is a hyperglycemia-induced increase in oxidative stress. Reactive oxygen species (ROS) are produced by oxidative phosphorylation, nicotinamide adenine dinucleotide phosphate oxidase (NADPH), xanthine oxidase, the uncoupling of lipoxygenases, cytochrome P450 monooxygenases, and glucose autoxidation. Once formed, ROS deplete antioxidant defenses, rendering the affected cells and tissues more susceptible to oxidative damage. Lipid, DNA, and protein are the cellular targets for oxidation, leading to changes in cellular structure and function. Recent evidence suggests ROS are also important as second messengers in the regulation of intracellular signaling pathways and, ultimately, gene expression. This review explores the production of ROS and the propagation and consequences of oxidative stress in diabetes.     

Determination of urinary malondialdehyde by isotope dilution LC-MS/MS with automated solid-phase extraction: a cautionary note on derivatization optimization

A highly sensitive quantitative LC-MS/MS method was developed for measuring urinary malondialdehyde (MDA). With the use of an isotope internal standard and online solid-phase extraction, urine samples can be directly analyzed within 10 min after 2,4-dinitrophenylhydrazine (DNPH) derivatization. The detection limit was estimated as 0.08 pmol. This method was further applied to assess the optimal addition of DNPH for derivatization and to measure urinary MDA in 80 coke oven emission (COE)-exposed and 67 nonexposed workers. Derivatization optimization revealed that to achieve complete derivatization reaction, an excess of DNPH is required (DNPH/MDA molar ratio: 893-8929) for urine samples that is about 100 times higher than that of MDA standard solutions (molar ratio: 10-80). Meanwhile, the mean urinary concentrations of MDA in COE-exposed workers were significantly higher than those in nonexposed workers (0.23±0.17 vs 0.14±0.05 μmol/mmol creatinine, P<0.005). Urinary MDA concentrations were also significantly associated with the COE (P<0.005) and smoking exposure (P<0.05). Taken together, this method is capable of routine high-throughput analysis and accurate quantification of MDA and would be useful for assessing the whole-body burden of oxidative stress. Our findings, however, raise the issue that derivatization optimization should be performed before it is put into routine biological analysis.     

Oxidative stress and the development of diabetic retinopathy: Contributory role of matrix metalloproteinase-2

Matrix metalloproteinases (MMPs) degrade extracellular matrix and regulate many functions including cell signaling. Oxidative stress is implicated in the development of diabetic retinopathy, and MMP-2, the most ubiquitous member of the MMP family, is sensitive to oxidative stress. This study aimed to determine the regulation of MMP-2 by oxidative stress in the development of diabetic retinopathy and the role of MMP-2 in the apoptosis of retinal capillary cells. The effects of mitochondrial superoxide scavenger on glucose-induced alterations in MMP-2, and its proenzyme activator MT1-MMP and physiological inhibitor TIMP-2, were determined in retinal endothelial cells, and the regulation of their glucose-induced accelerated apoptosis by the inhibitors of MMP-2 was accessed. To confirm in vitro results, the effects of antioxidant supplementation on MMP-2, MT1-MMP, and TIMP-2 were investigated in the retina of streptozotocin-induced diabetic rats. Glucose-induced activation of retinal capillary cell MMP-2 and MT1-MMP and decrease in TIMP-2 were inhibited by superoxide scavengers, and their accelerated apoptosis was prevented by the inhibitors of MMP-2. Antioxidant therapies, which have been shown to inhibit oxidative stress, capillary cell apoptosis, and retinopathy in diabetic rats, ameliorated alterations in retinal MMP-2 and its regulators. Thus, MMP-2 has a proapoptotic role in the loss of retinal capillary cells in diabetes, and the activation of MMP-2 is under the control of superoxide. This suggests a possible use of MMP-2-targeted therapy to inhibit the development of diabetic retinopathy.     

Reduction of DNA fragmentation and hydroxyl radical production by hyaluronic acid and chondroitin-4-sulphate in iron plus ascorbate-induced oxidative stress in fibroblast cultures

Glycosaminoglycans (GAGs), components of extracellular matrix, are thought to play important roles in cell proliferation and differentiation in the repair process of injured tissue. Oxidative stress is one of the most frequent causes of tissue and cell injury and the consequent lipid peroxidation is the main manifestation of free radical damage. It has been found to play an important role in the evolution of cell death. Since several reports have shown that hyaluronic acid (HYA) and chondroitin-4-sulphate (C4S) are able to inhibit lipid peroxidation during oxidative stress, We investigated the antioxidant capacity of these GAGs in reducing oxidative damage in fibroblast cultures.

Free radicals production was induced by the oxidizing system employing iron (Fe₂₊) plus ascorbate. We evaluated cell death, membrane lipid peroxidation, DNA damage, protein oxidation, hydroxyl radical (OH_•) generation and endogenous antioxidant depletion in human skin fibroblast cultures.

The exposition of fibroblasts to FeSO₄ and ascorbate caused inhibition of cell growth and cell death, increased OH_• production determined by the aromatic trap method; furthermore it caused DNA strand breaks and protein oxidation as shown by the DNA fragments analysis and protein carbonyl content, respectively. Moreover, it enhanced lipid peroxidation evaluated by the analysis of conjugated dienes (CD) and decreased antioxidant defenses assayed by means of measurement of superoxide dismutase (SOD) and catalase (CAT) activities.

When fibroblasts were treated with two different doses of HYA or C4S a protective effect, following oxidative stress induction, was shown. In fact these GAGs were able to limit cell death, reduced DNA fragmentation and protein oxidation, decreased OH_• generation, inhibited lipid peroxidation and improved antioxidant defenses.

Our results confirm the antioxidant activity of HYA and C4S and this could represent a useful step in the understanding of the exact role played by GAGs in living organisms.     

Effect of vitamin E and eccentric exercise on selected biomarkers of oxidative stress in young and elderly men

Muscle damage resulting from eccentric exercise provides a useful model of oxyradical-induced injury and can be used to examine age-related responses to oxidative stress. Sixteen young (26.4 ± 3.3 years) and 16 older (71.1 ± 4.0 years) healthy men were randomly assigned to 1000 IU/d vitamin E or placebo for 12 weeks and ran downhill for 45 min at 75% VO₂max, once before and following supplementation. Blood samples were obtained before (baseline) and immediately postexercise (0 h), and at 6, 24, and 72 h postexercise to determine antioxidant status, muscle damage, lipid peroxidation, and DNA damage. Following exercise, young and older men experienced similar increases in serum creatine kinase (CK), F₂-isoprostanes (iPF₂; p < .001) and malondialdehyde (MDA; p < .01), although iPF₂ peaked at 72 h postexercise and MDA peaked at 0 h. Oxygen Radical Absorbance Capacity (ORAC) decreased at 72 h (p < .01) and correlated with the rise in iPF₂, MDA, and CK in the young men (p < .05). Leukocyte 8-hydroxy-2′-deoxyguanosine (8-OHdG) was unaffected by exercise. Vitamin E decreased peak CK in young men, while in older men it decreased resting levels of iPF₂ and suppressed the 24 h postexercise increases in iPF₂ (p < .05). Thus, vitamin E supplementation induced modest changes eccentric exercise-induced oxidative stress, although differentially between the young and older subjects, while age had no direct influence on these responses among this group of physically fit subjects.     

Protective effect of arginine on oxidative stress in transgenic sickle mouse models

Sickle cell disease (SCD) is characterized by reperfusion injury and chronic oxidative stress. Oxidative stress and hemolysis in SCD result in inactivation of nitric oxide (NO) and depleted arginine levels. We hypothesized that augmenting NO production by arginine supplementation will reduce oxidative stress in SCD. To this end, we measured the effect of arginine (5% in mouse chow) on NO metabolites (NOx), lipid peroxidation (LPO), and selected antioxidants in transgenic sickle mouse models. Untreated transgenic sickle (NY1DD) mice (expressing  75% β^S-globin of all β-globins; mild pathology) and knockout sickle (BERK) mice (expressing exclusively hemoglobin S; severe pathology) showed reduced NOx levels and significant increases in the liver LPO compared with C57BL mice, with BERK mice showing maximal LPO increase in accordance with the disease severity. This was accompanied by reduced activity of antioxidants (glutathione, total superoxide dismutase, catalase, and glutathione peroxidase). However, GSH levels in BERK were higher than in NY1DD mice, indicating a protective response to greater oxidative stress. Importantly, dietary arginine significantly increased NOx levels, reduced LPO, and increased antioxidants in both sickle mouse models. In contrast, nitro-L-arginine methylester, a potent nonselective NOS inhibitor, worsened the oxidative stress in NY1DD mice. Thus, the attenuating effect of arginine on oxidative stress in SCD mice suggests its potential application in the management of this disease.     

Trace elements,oxidative stress and glycemic control in young people with type 1 diabetes mellitus

Trace elements and oxidative stress are associated with glycemic control and diabetic complications in type 1 diabetes mellitus. In this study, we analyzed the levels of serum copper, zinc, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and urinary MDA and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in 33 type 1 diabetic patients with optimal and suboptimal glycemic control (HbA_1C < 9.0%) and 40 patients with poor glycemic control (HbA_1C ≥ 9%) and 27 age- and sex-matched non-diabetic controls to evaluate the differences between these markers in different glycemic control states. Diabetic patients, especially poor-glycemic-control subjects (HbA_1C ≥ 9%), exhibited significantly lower levels of serum zinc and increased levels of serum copper (and, therefore, increased serum copper-to-zinc ratios), serum SOD, blood MDA, and urinary MDA and 8-OHdG, relative to non-diabetic subjects. Furthermore, significant correlations existed in these patients between the serum copper, serum copper-to-zinc ratio, and urinary MDA (all p < 0.001) and the levels of urinary 8-OHdG (p = 0.007) and HbA_1C. Our results suggest that high serum copper levels and oxidative stress correlate with glycemic control. Therefore, strict glycemic control, decreased oxidative stress, and a lower copper concentration might prevent diabetic complications in patients with type 1 diabetes mellitus.     

Reductive stress in young healthy individuals at risk of Alzheimer disease

Oxidative stress is a hallmark of Alzheimer disease (AD) but this has not been studied in young healthy persons at risk of the disease. Carrying an Apo ε4 allele is the major genetic risk factor for AD. We have observed that lymphocytes from young, healthy persons carrying at least one Apo ε4 allele suffer from reductive rather than oxidative stress, i.e., lower oxidized glutathione and P-p38 levels and higher expression of enzymes involved in antioxidant defense, such as glutamylcysteinyl ligase and glutathione peroxidase. In contrast, in the full-blown disease, the situation is reversed and oxidative stress occurs, probably because of the exhaustion of the antioxidant mechanisms just mentioned. These results provide insights into the early events of the progression of the disease that may allow us to find biomarkers of AD at its very early stages.     

Mitochondrial DNA mutations and oxidative damage in skeletal muscle of patients with chronic uremia

Abundant evidence has been gathered to suggest that mitochondrial DNA (mtDNA) sustains many more mutations and greater oxidative damage than does nuclear DNA in human tissues. Uremic patients are subject to a state of enhanced oxidative stress due to excess production of oxidants and a defective antioxidant defense system. This study was conducted to investigate mtDNA mutations and oxidative damage in skeletal muscle of patients with chronic uremia. Results showed that large-scale deletions between nucleotide position (np) 7,900 and 16,300 of mtDNA occurred at a high frequency in muscle of uremic patients. Among them, the 4,977-bp deletion (mtDNA⁴⁹⁷⁷) was the most frequent and most abundant large-scale mtDNA deletion in uremic skeletal muscle. The proportion of mtDNA⁴⁹⁷⁷ was found to correlate positively with the level of 8-hydroxy 2-deoxyguanosine (8-OHdG) in the total DNA of skeletal muscle (r=0.62, p<0.05). Using long-range PCR and DNA sequencing, we identified and characterized multiple deletions of mtDNA in skeletal muscle of 16 of 19 uremic patients examined. The 8,041-bp deletion, which occurred between np 8035 and 16,075, was flanked by a 5-bp direct repeat of 5-CCCAT-3. Some of the deletions were found in more than 1 patient. On the other hand, we found that the mean 8-OHdG/10⁵ dG ratio in the total cellular DNA of muscle of uremic patients was significantly higher than that of the controls (182.7 ± 63.6 vs. 50.9 ± 21.5, p=0.05). In addition, the mean 8-OHdG/10⁵ dG ratio in muscle mtDNA of uremic patients was significantly higher than that in nuclear DNA (344.0 ± 56.9 vs. 146.3 ± 95.8, p=0.001). Moreover, we found that the average content of lipid peroxides in mitochondrial membranes of skeletal muscle of uremic patients was significantly higher than that of age-matched healthy subjects (23.76 ± 6.06 vs. 7.67 ± 0.95 nmol/mg protein; p<0.05). The average content of protein carbonyls in the mitochondrial membranes prepared from uremic skeletal muscles was significantly higher than that in normal controls (24.90 ± 4.00 vs. 14.48 ± 1.13 nmol/mg protein; p<0.05). Taken together, these findings suggest that chronic uremia leads to mtDNA mutations together with enhanced oxidative damage to DNA, lipids, and proteins of mitochondria in skeletal muscle, which may contribute to the impairment of mitochondrial bioenergetic function and to skeletal myopathy commonly seen in uremic patients.     

In vitro alpha-amylase inhibition and in vivo antioxidant potential of Momordica dioica seeds in streptozotocin-induced oxidative stress in diabetic rats

Momordica dioica Roxb. Commonly known as “Kakora” in Telugu, is used in the Indian traditional system of medicine for the treatment of diabetes. The aim of this study was to investigate the antidiabetic activity of methanolic extract of M. dioica seeds (MEMD) in streptozotocin (STZ) induced diabetic rats. The in vitro α-amylase inhibitory activity of the MEMD was done by spectrophotometric method. Diabetes was induced by STZ (45 mg/kg; i.p), MEMD (100 & 200 mg/kg; b.wt) and standard drug metformin (50 mg/kg; b.wt) were administered to the diabetic rats. Blood glucose was estimated on the 11th day and the level of MDA, SOD and CAT was estimated in the liver tissue homogenate after the 15 days of experimental period. MEMD showed significant inhibition of alpha amylase activity and the IC₅₀ was found to be 48 μg/ml. Oral administration of MEMD significantly reduced blood glucose level (P < 0.05), diminished the MDA level and refurbished depleted antioxidant enzymes and Insulin level to normalcy. These findings revealed that M. dioica seeds possess antihyperglycemic, antioxidant and anti lipid peroxidative activity and thus mitigate STZ-induced oxidative damage.     

Ameliorative effects of Anchomanes difformis aqueous extract against oxidative stress in the testes and epididymis of streptozotocin-induced diabetic male Wistar rats

Hyperglycemia is a central trait of diabetes mellitus (DM) and is linked to an increase in free radical generation and oxidative stress in the testes, resulting in testicular tissue damage and male infertility. Synthetic medicines are commonly used to manage diabetes; however, they are costly and associated with adverse effects. As a result, the search for a safer and affordable alternative from medicinal plants that contain antioxidants has become imperative to scavenge free radicals caused by hyperglycaemia, thereby alleviating male reproductive dysfunction. Therefore, the present aimed to investigate the ameliorative effects of Anchomanes difformis aqueous extract against oxidative stress in the testes and epididymis of streptozotocin-induced diabetic male Wistar rats. A total of 64 male Wistar rats (eight weeks old) weighing 180 ± 10 mg/kg were divided into seven groups at random. Type 2 diabetic mellitus (T2DM) was induced by streptozotocin (STZ) and a 10% fructose injection intraperitoneally using 40 mg/kg body weight rats. The levels of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) activity, reduced glutathione (GSH) concentration, and ferric reducing antioxidant (FRAP) as well as 2, 2-diphenyl-1-picrylhydrazyl (DPPH) values were used to establish the testicular oxidative status. It was found that A. difformis extract significantly (p < 0.05) lowered MDA levels in diabetic rats. Both CAT and SOD activity were significantly (p < 0.05) lower following induction of DM and increased (p < 0.05) after treating with A. difformis. The findings of this study show that A. difformis extract could be a promising source of lead compounds for the development of a therapeutic agent to treat male infertility caused by DM complications.