Protective effects of irbesartan and alpha lipoic acid in STZ-induced diabetic nephropathy in rats

The aim of this study was designed to investigate the possible beneficial effects of the angiotensin (ang) II T₁ (AT₁) receptor blocker, irbesartan (Irb), and the alpha lipoic acid (ALA) in streptozotocin (STZ)-induced diabetic nephropathy (DNP) in rats. The rats were randomly allotted into one of five experimental groups: A, control; B, diabetic untreated; C, diabetic treated with Irb; D, diabetic treated with ALA; and E, diabetic treated with Irb + ALA; each group contains 10 animals. B, C, D, and E groups received STZ. Diabetes was induced in four groups by a single intraperitoneal injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). The rats in Irb-, ALA-, and Irb + ALA-treated groups were given Irb (5 mg/kg), ALA (in a dose of 3 mg/kg), and Irb + ALA (in a dose of 2.5 + 1.5 mg/kg) once a day orally by using intragastric intubation for 12 weeks starting 2 days after STZ injection, respectively. Treatment with ALA and especially Irb reduced the glomerular size; thickening of capsular, glomerular, and tubular basement membranes; increased amounts of mesangial matrix and tubular dilatation as compared with diabetic-untreated rats. Notably, the better effects were obtained when Irb and ALA were given together. We conclude that Irb, ALA, and especially Irb + ALA therapy causes renal morphologic improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of Irb and ALA treatment, alone or its combination, may indicate its usefulness as a potential treatment in DNP.     

Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Type 1 Receptor Blockade on Streptozotocin-Induced Diabetic Nephropathy

The aim of this study was designed to investigate the possible beneficial effects of the angiotensin-converting enzyme (ACE) inhibitor, Quinapril (Q) and, the angiotensin (ang) II T₁ (AT1) receptor blocker, irbesartan (Irb), in streptozotocin (STZ)-induced diabetes in rats. The rats were randomly allotted into one of five experimental groups: A (control), B (diabetic untreated), C (diabetic treated with Q), D (diabetic treated with Irb), and E (diabetic treated with Q&Irb), each group containing 10 animals. Groups B–E received STZ. Diabetes was induced in four groups by a single intraperitoneal (i.p) injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). Two days after STZ treatment, development of diabetes in four experimental groups was confirmed by measuring blood glucose levels in a tail vein blood samples. Rats with blood glucose levels of 250 mg/dL or higher were considered to be diabetic. The rats in Q-, Irb-, and Q&Irb-treated groups were given Q (in a dose of 3 mg/kg body weight), Irb (5 mg/kg body weight), and Q&Irb (in a dose of 1.5 mg/kg + 2.5 mg/kg body weight) once a day orally by using intra-gastric intubation for 12 weeks starting two days after STZ injection. Treatment of Q and especially Irb reduced the glomerular size and thickening of capsular, glomerular, and tubular basement membranes; and increased amounts of mesangial matrix and tubular dilatation and renal function as compared with diabetics untreated. Notably, the better effects were obtained when Q and Irb given together. We conclude that Q, Irb, and especially Q+Irb therapy causes renal morphologic and functional improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of Q and Irb treatment, alone or its combination, may indicate its usefulness as a potential treatment in diabetic nephropathy (DNp).     

Effect of Vitamin E Supplementation on Various Functional Properties of Macrophages and Neutrophils Obtained from Weaned Piglets

Sixteen piglets were used to determine the effect of vitamin E supplementation on several functional properties of macrophages and neutrophils obtained from weaned piglets. Piglets, immediately following weaning, were assigned to one of three experimental groups: control (no vitamin E supplementation), low level of vitamin E supplementation (100 mg dl ‐α‐tocopheryl acetate/kg diet) and high level of vitamin E supplementation (300 mg dl ‐α‐tocopheryl acetate/kg diet). Supplementation of vitamin E lasted for a period of 36 days, following a 3‐day adaptation period after weaning. Blood samples were collected on days 0, 12, 24 and 36 of the experimental period, monocytes/macrophages and neutrophils were isolated and the following parameters were determined in macrophages and neutrophils activated by phorbol myristate acetate: total cell‐associated and membrane‐bound urokinase plasminogen activator (u‐PA) activity and superoxide anion production. Results showed that macrophages and neutrophils isolated from piglets that received supplemental vitamin E had higher (P < 0.05) total and membrane‐bound u‐PA activities as well as higher (P < 0.05) superoxide anion production compared with the values of the corresponding cells obtained from control piglets on day 12 of the experimental period. Both levels of vitamin E supplementation (low and high) were equally effective. In contrast, vitamin E supplementation had no effect (P > 0.05) on total and membrane‐bound u‐PA activities and superoxide anion production by porcine macrophages and neutrophils on days 24 and 36 of the experimental period. In conclusion, the low level of vitamin E supplementation is recommended for piglets for the first 2 weeks after weaning.     

Effect of Kaempferia parviflora on sexual performance in streptozotocin‐induced diabetic male rats

Kaempferia parviflora Wall. Ex.Baker or Krachidum (KP) has been used locally in medicine and food. It has been claimed that KP has aphrodisia properties; however, no scientific data in support of this function in diabetic model have been reported. This study aimed to investigate the efficacy of KP on sexual behaviour and sperm parameter in streptozotocin (STZ)‐induced diabetic male rats. Diabetes was induced in twenty male rats by STZ and divided into four groups: diabetic control group, and 3 treatment groups where KP was dose at 140, 280 and 420 mg/kg orally once a day for 6 weeks. Five normal control rats were treated with vehicle. The body weight, blood glucose, food intake, epididymal sperm parameter, sexual behaviour and serum testosterone level were evaluated. The results showed that KP treatment has no effect on the body weight, blood glucose and food intake in diabetic rats. A significant increase in sperm density in diabetic rats was observed (p < .05) at highest dose of KP. Furthermore, KP treatment demonstrated a significant recovery of sexual behaviour and serum testosterone levels in diabetic rats. These results confirm that KP exhibits aphrodisiac properties that improve the sperm density, testosterone level and sexual performance of STZ‐induced diabetic rats.     

Effect of Vitamin E Supplementation on Lymphocyte Distribution in Gut‐Associated Lymphoid Tissues Obtained from Weaned Piglets

Fifteen piglets were used to determine the effect of vitamin E supplementation on the number of CD4‐immunoreactive (CD4+) T‐lymphocytes, CD8‐immunoreactive (CD8+) T‐lymphocytes and IgA‐immunoreactive (IgA+) B‐lymphocytes per follicle in the Peyer's patch of distal ileum and the mesenteric lymph nodes of weaned piglets. Piglets, following a 3‐day adaptation period after weaning, were assigned to one of three experimental groups: control (no vitamin E supplementation), vitamin E supplementation of 100 mg/kg of diet and vitamin E supplementation of 300 mg/kg of diet. Supplementation of vitamin E lasted for a period of 36 days. The basal diet contained 80 mg α‐tocopherol/kg of diet. All piglets were killed at day 39 after weaning and samples of the distal ileum and adjacent mesenteric lymph nodes were collected. The number of cells for each lymphocyte subset was counted in the Peyer's patch and the mesenteric lymph nodes follicles, in cryostat sections processed for immunohistochemistry. Results showed that vitamin E supplementation (300 mg/kg diet) of piglets caused an increase (P < 0.05) in the number of IgA+ B‐lymphocytes in the Peyer's patch, but not in the mesenteric lymph nodes, compared with the corresponding values in control animals. Vitamin E supplementation had no effect (P > 0.05) on the number of CD4+ and CD8+ T‐lymphocytes in the follicles of the Peyer's patch and the adjacent mesenteric lymph nodes. Thus, vitamin E had relatively minor effects on distribution of the major immunocompetent cells in the gut. The numbers of CD4+ and CD8+ T‐lymphocytes as well as IgA+ B‐lymphocytes per follicle were higher by 26–77% (P < 0.05) in the mesenteric lymph nodes than the corresponding values in the Peyer's patch.     

Prostaglandin E1 alleviates neuropathic pain and neural dysfunction from entrapment neuropathy associated with diabetes mellitus

In this report, we present the results of investigation of the effects of prostaglandin E1 (PGE1) on entrapment neuropathy using a diabetic rat. A total of 60 male Sprague‐Dawley rats were used in the study. The model of tibial nerve entrapment neuropathy associated with diabetes mellitus was created by streptozotocin‐induced diabetic rats reared in cages with wire grid flooring. Rats were assigned to four groups: nondiabetic (n = 15), untreated diabetic (n = 15), diabetic treated with 30 μg/kg PGE1 (n = 15), and diabetic treated with 100 μg/kg PGE1 (n = 15). Pain tests and electrophysiological tests were performed at 0, 2, and 4 weeks, and assessments of gait, histology, and mRNA expression levels were performed at 4 weeks after initiating the PGE1 administration. In the 30 and 100 μg groups, the mechanical withdrawal thresholds measured by pain tests at 4 weeks (36.2 ± 16.4 g and 31.7 ± 15.3 g, respectively) and the motor conduction velocity (24.0 ± 0.2 m/s and 24.4 ± 0.3 m/s, respectively) were significantly higher than the untreated diabetic group (all P < 0.05) and lower than the nondiabetic group (all P < 0.001). In the gait analysis, the mean intensities in the 30 and 100 μg group (128.0 ± 20.1 a.u. and 109.0 ± 27.8 a.u., respectively) were significantly higher than the untreated diabetic (P < 0.01) and were not significantly different from the nondiabetic group (P = 0.81). Fiber density (P = 0.46) and fiber diameter (P = 0.15) did not show any significant differences. PGE1 significantly decreased nerve growth factor (NGF) mRNA and increased vascular endothelial growth factor (VEGF) mRNA in the tibial nerve (both P < 0.01). In conclusion, neurological deteriorations of diabetic rats were alleviated with PGE1, which is associated with inhibition of NGF and enhancement of VEGF at the entrapment site. © 2014 Wiley Periodicals, Inc. Microsurgery 34:568–575, 2014.     

Protective effect of vitamin E and vitamin C alone and in combination on testicular damage induced by sodium metabisulphite in rats: A stereological study

The existing investigation was directed to consider the protective role of vitamin C and E alone and in combination on sodium metabisulphite‐induced damage on testicular. Experimental animals were received sodium metabisulphite (520 mg/kg) alone and in combination with vitamin E (100 mg/kg), vitamin C (100 mg/kg) and vitamin E + C, while the control groups received 0.9% saline solution and olive oil (the solvent of the vitamin E). Finally, the changes in the testis histology were examined stereologically. Lipid peroxidation was assessed through the measurement of malondialdehyde (MDA) levels in testis tissues. Also, serum testosterone concentrations were measured. The results indicated that 80%–90% (spermatogonia A and B, spermatocyte and Leydig) and 40% of the Sertoli cells were missed in the rats that received sodium metabisulphite, respectively, compared with the controls. The co‐supplementation of vitamin E with vitamin C significantly decreased MDA (p = 0.006) and increased testosterone (p = 0.001) concentrations in the rats received SMB which were as much as control and olive groups. Co‐supplementation of vitamin E and vitamin C due to their synergistic effects could be an appropriate strategy in preventing testicular from sodium metabisulphite‐induced damage.     

Effects of Vitamin E and Different Energy Sources on Vitamin E Status,Milk Quality and Reproduction in Transition Cows*

We investigated whether vitamin E supplementation and supplemental energy sources (fat or starch) influenced plasma and milk levels of vitamin E, and reproductive and other parameters in 28 Italian Friesian multiparous dry cows. From 14 days before expected calving to 7 days after, the animals were assigned to either basal diet (containing 1000 IU/day of vitamin E) or an extra 1000 IU/day of vitamin E (total 2000 IU). In addition they received either 0.5 kg/day of corn or 0.2 kg/day of calcium soaps. Plasma samples were collected 4 days before expected calving and 4 days after calving and analysed for α‐tocopherol and cholesterol. Milk yield as well as the composition, somatic cell count (SCC) and α‐tocopherol of milk were determined 7 and 14 days after calving. Milk yield and composition were unaffected by treatments. SCC was significantly lower in (SCC Log 4.62 versus Log 5.1, P < 0.01) 2000 IU/day animals than in the 1000 IU/day group. Milk α‐tocopherol was higher (P < 0.001) in animals receiving 2000 IU/day (1.11 vs. 0.65 µg/ml, P < 0.01). Plasma α‐tocopherol in animals receiving 2000 IU/day was also higher (P < 0.001) than in cows receiving 1000 IU/day (4.85 vs. 3.25 µg/ml), but was not affected by dietary energy source. Number of services and days to conception were lower (P < 0.01) in the 2000 IU vitamin E supplemented cows. To conclude, dietary vitamin E supplementation to periparturient dairy cows increased plasma and milk vitamin E, decreased SCC in milk, and improved fertility but different energy sources had no effect on any measured variable.     

Zingiber officinale preserves testicular structure and the expression of androgen receptors and proliferating cell nuclear antigen in diabetic rats

The aim of this study was to assess the efficacy of Zingiber officinale, commonly referred to as ginger, in preserving the structural integrity of testis in streptozotocin (STZ)-induced diabetic rats compared to the efficacy of metformin, the traditional effective antidiabetic drug. STZ was utilised for the induction of diabetes mellitus in male Sprague Dawley rats. The study included five groups (n = 6 each), namely the normal control, ginger-treated normal, nontreated diabetic, metformin-treated diabetic and ginger-treated diabetic groups. Biochemical assessment of fasting blood glucose level (BGL) and total antioxidant capacity (TAC) was performed. Histopathological assessment of the testes was performed using routine and immunohistochemical techniques. Fasting BGL significantly (p = .01) reduced, whereas TAC significantly increased (p < .001) in metformin- and ginger-treated diabetic rats compared to those in untreated diabetic rats. Metformin and ginger reduced the degenerative changes observed in the testes of diabetic rats, significantly reduced (p < .001) caspase-3 immunoexpression, and significantly increased (p < .001) the immune-expression of androgen receptors and proliferating cell nuclear antigen. Ginger has antidiabetic effects and preserves testicular structural integrity and, thus, is recommended as an adjuvant therapy for male diabetic patients in the reproductive period.     

Effect of kolaviron,a biflavonoid complex from Garcinia kola seeds,on the antioxidant,hormonal and spermatogenic indices of diabetic male rats

The antihyperglycaemic effect of kolaviron (KV), a biflavonoid from Garcinia kola has been established in previous studies. In this study, we investigated the effect of KV (200 mg kg^?1) on the antioxidant, hormonal and spermatogenic indices of alloxan‐diabetic male rats, and metformin hydrochloride (MET) (30 mg kg^?1) served as standard drug. The results showed that KV and MET significantly (P < 0.05) decreased the fasting blood glucose of the diabetic rats. Also, untreated and MET‐treated diabetic groups had significantly (P < 0.05) lower body‐weight gain and relative weights of testes. In addition, epididymal sperm abnormalities were increased, whereas sperm count, motility, testicular protein and sialic acid were decreased in untreated diabetic group. Also, antioxidant parameters, reduced glutathione, catalase, superoxide dismutase, glutathione‐S‐transferase and glutathione peroxidase were significantly (P < 0.05) reduced in the testes with a concomitant increase in lipid peroxidation in untreated diabetic group. Furthermore, untreated diabetic group had significantly (P < 0.05) lower levels of testosterone, luteinising and follicle‐stimulating hormones relative to controls. Treatment with KV restored the relative weights of testes, activities of antioxidant enzymes, sperm and hormonal indices of the diabetic animals. This study demonstrated the role of KV to promote fertility in diabetic male rats by enhancing the hormonal and antioxidant status of the rats.     

The Puerarin improves renal function in STZ-induced diabetic rats by attenuating eNOS expression

Abstract

Diabetic nephropathy (DN) is a serious complication and it leads to kidney failure. The endothelial nitric oxide synthases (eNOS) seems to be involved in the development and progression of DN. The Puerarin is a well-known Chinese traditional formula, which is widely used in clinical practice for the treatment of kidney disease. The present study was designed to investigate the renal protective effects of Puerarin on streptozotocin (STZ)-induced diabetic rats. Thirty Sprague–Dawley (SD) male rats were divided into three groups at random. The diabetic group and the Puerarin-treated group were intraperitoneally injected with STZ 65?mg/kg and the Puerarin-treated rats were intraperitoneally injected Puerarin 100?mg/kg/day for 4 weeks. The results showed the Puerarin could improve body weight, blood sugar, BUN and SCr levels, and reduce ultrastructural changes of kidney in diabetic rats. It also attenuated eNOS expression in glomerular endothelial cells and tubular cells of diabetic rats with Puerarin treatment (p?<?0.05). The Puerarin had significant renal-protective effects for the diabetic nephropathy, possibly through regulating eNOS expression, and it may be used as a potential therapeutic reagent.     

Quercetin and vitamin E attenuate diabetes-induced testicular anomaly in Wistar rats via the mitochondrial-mediated apoptotic pathway

The role of quercetin and vitamin E treatment against streptozotocin (STZ)-induced testicular abnormalities in diabetic rats and the possible mechanism of action they use for protection were investigated. Diabetes was induced by STZ (45 mg/kg i.p. once) and blood glucose was determined. Plasmatic insulin, testosterone, luteinising hormone and follicle-stimulating hormone (FSH) were determined by ELISA. Levels of cytochrome c, caspase 3 and caspase 9 were evaluated by immunohistochemistry, while lesions were viewed by histology. Insulin played a role in testicular protection against male infertility through modulation of luteinising hormone (LH). This consequently increased Leydig and Sertoli cells and maturation of germ cells with the attached epididymis having abundant spermatozoa. The study showed a positive correlation in the levels of LH, FSH and testosterone; it was further established that all treatments normalised diabetes-induced alterations. Treatment with quercetin and vitamin E resulted in 34% decrease of apoptogenic cytochrome c release. This protected the testes against excessive apoptosis by decreasing caspase 3 and caspase 9 activation by up to 30 and 28% respectively (p < .05). Histology also showed that treatment prevented testicular cell death. The findings show that quercetin/vitamin E possess free radical scavenging properties that protected against testicular damage in diabetes. This suggests the possibility of pharmaco-therapeutic intervention.     

Association between vitamin D deficiency and diabetic foot ulcer wound in diabetic subjects: A meta-analysis

A meta-analysis was performed to evaluate the association between vitamin D deficiency and diabetic foot ulcer wounds in diabetic subjects. A systematic literature search up to March 2022 incorporated 7586 subjects with diabetes mellitus at the beginning of the study; 1565 were using diabetic subjects with foot ulcer wounds, and 6021 were non-ulcerated diabetic subjects. Statistical tools like the dichotomous and contentious method were used within a random or fixed-influence model to establish the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) to evaluate the influence of vitamin D deficiency in managing diabetic foot ulcer wound. Diabetic subjects with foot ulcer wounds had significantly lower vitamin D levels (MD, −6.48; 95% CI, −10.84 to −2.11, P < .004), higher prevalence of vitamin D deficiency (<50 nmoL/L) (OR, 1.82; 95% CI, 1.32-2.52, P < .001), and higher prevalence of severe vitamin D deficiency (OR, 2.53; 95% CI, 1.65-3.89, P < .001) compared with non-ulcerated diabetic subjects. Diabetic subjects with foot ulcer wounds had significantly lower vitamin D levels, higher prevalence of vitamin D deficiency, and higher prevalence of severe vitamin D deficiency compared with non-ulcerated diabetic subjects. Further studies are required to validate these findings.     

Corrective role of Eugenia jambolana on testicular impairment in streptozotocin‐induced diabetic male albino rat: An approach through genomic and proteomic study

The present study was conducted to explore the effect of ethyl acetate fraction of hydro‐methanolic (40 : 60) extract of seed of Eugenia jambolana on testicular impairment in diabetic rats. In this respect, biomarkers of oxidative stress, genomics and proteomics in testicular tissue were assessed. Side by side, glycated haemoglobin, serum testosterone, activities of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase in serum, epididymal sperm count including reproductive organosomatic indices were evaluated. Results indicate that a significant recovery (P < 0.05) in the levels of these parameters in fraction‐treated diabetic group in comparison with diabetic control. A significant recovery was noted (P < 0.05) in the expression of Bax and Bcl‐2 gene towards the control after the treatment of said fraction. Histological study also focused a significant recovery (P < 0.05) in the number of different generation of germ cells at stage VII of spermatogenesis in fraction‐treated diabetic group. The said fraction treatment to diabetic rat can recover the activities of serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase significantly towards the control (P < 0.05). Finally, it may be concluded that ethyl acetate fraction of seed of E. jambolana has a promiseable remedial effect on diabetes‐induced testicular dysfunctions in male rat without inducing any metabolic toxicity.     

Rutin,an antioxidant flavonoid,induces glutathione and glutathione peroxidase activities to protect against ethanol effects in cadmium‐induced oxidative stress in the testis of adult rats

Exposure to cadmium (Cd) reduces sperm quality and induces oxidative stress in the testis. Rutin is an effective antioxidant flavonoid. We studied the effect of ethanol (EtOH, 5 g/kg b.wt.) intake on Cd (50 mg/kg b.wt.)‐induced testicular toxicity with or without RUT pre‐treatment (25, 50, 100 mg/kg b.wt.) in rats. At the end of the 15‐day oral treatment, co‐treatment with EtOH decreased the activities of glutathione (GSH), GSH‐peroxidase and superoxide dismutase resulting to slight increase in the testicular MDA level compared to Cd‐treated rats. The Cd+EtOH animals had higher levels of abnormal spermatozoa, decreased epididymal sperm number and serum testosterone levels (p < .05) compared to the Cd‐treated animals. Rutin co‐administration protected against the EtOH effects in a dose‐dependent manner, with the Cd+EtOH+50 mg/kg RUT‐ and Cd+EtOH+100 mg/kg RUT‐treated animals having higher GSH and GSH‐Px activities beyond the control values (p < .05). In a supplementary study, animals treated daily with RUT alone (25, 50, 100 mg/kg b.wt.) for 15 days dose‐dependently increased testicular GSH‐peroxidase and GSH activities by 9.38%, 31.25%, 56.25% and 7.14%, 32.14%, 60.71%, respectively, compared to control values. Therefore, RUT induces GSH and GSH‐Px activities to protect against Cd+EtOH‐induced testis oxidative stress in rats.     

The effect of vitamin A on the course of renal ablation nephropathy

Renal scarring due to pyelonephritis was shown to improve in rats given vitamin A. We evaluated the effect of vitamin A in a renal ablation nephropathy model. Four groups, each including 7 rats with 5/6 nephrectomy, were formed: group I (no vitamin A), group II (60 kIU vitamin A), group III (120 kIU vitamin A), and group IV (180 kIU vitamin A). Four sham-operated rats comprised the control group. After 6 weeks of 5/6 nephrectomy, the rats were sacrificed and serum creatinine, vitamin A, and β-carotene levels were determined in addition to histopathological evaluation of the remnant kidneys. The tubulointerstitial and glomerular changes were graded as ”0–3” and ”0–5” respectively, in accordance with the severity of the lesions. Tubulointerstitial score (TIS), mean glomerulosclerosis score (MGS, arithmetical mean of the sclerosis scores of 100 glomeruli), and severity of glomerulosclerosis index (SGI, ratio of the number of glomeruli with grade ≥3 sclerosis to the total number of glomeruli examined) were calculated for each rat. Serum creatinine levels were higher in the study groups than the control rats (P<0.05), but there was no significant difference between the study groups (although the levels increased as the dose of vitamin A increased). Serum vitamin A levels were significantly higher in the groups given vitamin A than the control rats and group I (P<0.05). In addition, serum vitamin A levels increased significantly in parallel to increasing doses of vitamin A (P<0.05). Serum β-carotene levels did not differ between the groups, except for group II, which had lower levels than controls (P=0.01). MGS and SGI were significantly higher in the study groups than control rats (P<0.05), but did not differ between the study groups. Study and control rats were not different with respect to TIS, but there was a difference between the control group and group III (P=0.04). Group II had the lowest MGS, SGI, and TIS scores among the study groups. When all the rats were considered together, vitamin A levels did not correlate with the MGS and SGI, but correlated positively with the TIS (r=0.391, P=0.027). β-Carotene levels also did not correlate with the MGS, SGI, and TIS. In conclusion, vitamin A administration did not significantly affect the clinical and pathological course of renal ablation nephropathy in rats. Furthermore, higher doses of vitamin A might even damage renal tissue. Received: 14 June 1999 / Revised: 2 December 1999 / Accepted: 2 December 1999     

Effect of p‐coumaric acid on the erectogenic enzyme activities and non‐protein thiol level in the penile tissue of normal and doxorubicin‐induced oxidative stress male rat

This study investigated effect of p‐coumaric acid (PCA) on erectogenic enzyme activity and non‐protein thiol level in the penile tissue of normal and doxorubicin (DOX)‐induced oxidative stress male rat. Sixty‐four (64) adult male rats weighing between 170 and 180 g were used for this work. After 14 days of acclimatisation, the rats were divided into eight groups (n = 8). Rats were orally pre‐treated with PCA dose dependently (50 and 100 mg/kg body weight [b.w.t]) and vitamin E (100 mg/kg b.w.t) for 14 days before induction with a single dose of DOX (15 mg/kg b.w.t, via i.p.). The result revealed that arginase, acetylcholinesterase (AChE), angiotensin‐I‐converting enzyme (ACE), phosphodiesterase‐5 (PDE‐5), adenosine monophosphohydrolase (AMPdase) activities were significantly (p < 0.05) higher in the DOX‐induced rats as against the control, which was significantly p < 0.05) higher when compared to normal rats treated with PCA. PCA also improved non‐protein thiol level in the penile tissue of both normal and DOX‐induced rats. Hence, this study revealed that PCA is capable of causing inhibitory effects on the activities of enzymes, associated with oxidative stress‐induced erectile dysfunction (ED) and could also be used as an aphrodisiac agent in the management/treatment of ED.     

Comparative analysis of the renoprotective effects of pentoxifylline and vitamin E on streptozotocin-induced diabetes mellitus

BACKGROUND: Oxidative stress (OxS) induced by diabetes plays an important role in the development of diabetic nephropathy. Studies have shown that antioxidants are beneficial in its reduction. Vitamin E has been documented as providing the most improvement in the antioxidative status. Recently, pentoxifylline (PTX) has been proposed to have antioxidant properties. AIM: The aim of the study was to assess the ability of two antioxidants to reduce lipid peroxidation and renal hypertrophy in vivo. METHODS: Diabetes was induced by streptozotocin (STZ) in rats. Treatment groups were divided as follows: healthy (H), diabetic without treatment (STZ), PTX treated group (STZ+PTX), and vitamin E supplemented (STZ+E) group. At 8 weeks, kidneys were removed; one was homogenized to quantify lipoperoxide levels (LPOS), and the other was used to study the morphological changes by electron microscopy (EM). Additionally, plasma total antioxidant activity (TAA) was quantified. Results: A reduction in LPOS was observed in both groups: PTX and vitamin E with regard to STZ group. PTX increased TAA compared to STZ+E, which restored it to its normal values. However, both treatments reduced the LPO/TAA ratio to lower basal levels; hence, similar results were obtained in terms of correcting functional parameters. Structural changes in STZ rats included a glomerular membrane thickening, podocyte flattening, as well as loss of fenestration in the endothelial layer. All these changes were less aggressive for treated rats. CONCLUSIONS: Vitamin E and PTX have potential therapeutic properties that may help to retard the rate of deterioration of diabetic kidneys.     

ICRF-187 (dextrazoxan) protects from adriamycin-induced nephrotic syndrome in rats

Background. Reactive oxygen species produced during metabolism of adriamycin are purported to play an important role in the pathogenesis of experimental adriamycin nephropathy in rats. ICRF-187 (dextrazoxan, Cardioxan), an iron chelator, has been shown to inhibit adriamycin-induced formation of hydroxyl radical and to decrease adriamycin cardiotoxicity in oncological patients. The aim of our study was to assess the putative protective role of ICRF-187 in adriamycin nephropathy by evaluating the possible participation of free radicals in its pathogenesis. Methods. We examined five experimental groups. Group A, received a single dose of adriamycin (5 mg/kg bw i.v.), group CA was given a single dose of ICRF-187 (100 mg/kg bw i.v.) before adriamycin administration, group CCA received a single dose of ICR-187 (100 mg/kg bw i.v.) before adriamycin administration followed by three weekly intraperitoneal injections (100 mg/kg bw) ICRF-187. Group CC received one dose of ICRF-187 (100 mg/kg bw i.v.) followed by three weekly intraperitoneal injections of ICRF-187, and group N served as control receiving saline. Common biochemical parameters, malondialdehyde (MDA) and antioxidant enzymes (glutathione peroxidase-GPx and superoxide dismutase-SOD) in blood and kidney homogenates were measured and histology of the kidney was studied after the rats were sacrificed. Results. Full-blown nephrotic syndrome developed after 3 weeks only in A rats. Nephrotic syndrome was completely prevented in all ICR-187 treated rats (CA, CCA). Proteinuria was significantly increased in A rats (108.2 + 48.4 mg/l of glomerular filtrate) compared with CA (12.4 + 6.8 mg/l, P <0.0001) and with N (6.1 + 3.5 mg/l, P < 0.0001). Total MDA in erythrocytes was significantly increased only in A rats (1.7 + 0.3 &mgr;mol/l) and was completely normalized by ICRF-187 in CA (1.1 + 0.2 &mgr;mol/l, P <0.001). Total TBARS and MDA in kidney homogenates were significantly elevated in groups with repeated administration of ICRF-187 (CC and CCA rats) compared to N, CA, A groups. Activity of GPx and SOD in kidney homogenate and in erythrocytes was not significantly increased by ICRF-187 in adriamycin treated rats. Histologic changes in A rats resembled minimal change nephropathy with fusion of foot processes and hyaline casts in tubules. There was only minimal mesangial proliferation and perivascular mast cell infiltrates in all groups of ICRF-187-treated rats. Conclusions. We conclude that ICRF-187, probably by chelation iron, completely protected rats from adriamycin-induced nephrotic syndrome. It supports the role of iron-mediated reactive oxygen species in the development of this type of glomerular injury. However, repeated administration of ICRF-187 alone is able to increase parameters of oxidative stress in the kidney.     

Resveratrol supplementation improves DNA integrity and sperm parameters in streptozotocin–nicotinamide‐induced type 2 diabetic rats

Reproductive dysfunction is one of the diabetes complications. Resveratrol, a polyphenol compound, shows antidiabetic and antioxidant effects. The aim of the present study was to investigate the protective effects of resveratrol on sperm parameters and chromatin quality in experimentally induced type 2 diabetes by streptozotocin and nicotinamide. Forty male adult Wistar rats were grouped into normal control, diabetic control and resveratrol‐treated diabetic groups (1, 5 and 10 mg/kg orally treated for 30 days). Type 2 diabetes was induced using a single dose of streptozotocin and nicotinamide by intraperitoneal injection. Then, the different parameters and chromatin condensation of the epididymal extracted spermatozoon were studied using aniline blue (AB), acridine orange (AO) and toluidine blue (TB) staining. The sperm parameters including count, motility and viability had significant reduction in diabetic rats (p < 0.05). Resveratrol increased count, motility and viable spermatozoa relative to the diabetic group (p < 0.05). The mean percentage of AB, AO and TB staining positive spermatozoa was increased in diabetic groups compared to control (p < 0.001) and decreased after treatment with 1 and 5 mg/kg resveratrol (p < 0.001). The results of AO and TB staining showed that resveratrol did not have any beneficial effect on chromatin condensation and denatured DNA at the dose of 10 mg/kg.