Panax ginseng protects against copper sulfate-induced kidney toxicity in rats

Amide hydrolysis of a novel chemical series of microsomal prostaglandin E synthase-1 inhibitors induces kidney toxicity in the rat.

To explore the effect mechanism of moxibustion with wheat-grain size cone at "Zusanli" (ST 36) on vascular injury and oxidative stress in hyperlipidemia through mammalian target of rapamycin (mTOR)/hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway. Forty healthy male SD rats with SPF grade were randomly divided into a normal group, a model group, a moxibustion group, and an inhibitor group, with 10 rats in each one. The hyperlipidemia model was established by feeding a high-fat diet for 8 weeks in rats of the model group, the moxibustion group and the inhibitor group. The moxibustion with wheat-grain size cone was delivered at bilateral "Zusanli" (ST 36) of each rat in the moxibustion group and the inhibitor group, with 3 cones on each acupoint in each intervention, once daily for 4 weeks. In the inhibitor group, before each intervention with moxibustion, rapamycin solution was injected intraperitoneally, 2.0 mg/kg. After modeling and intervention, using ELISA, the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in the serum of rats were determined. After intervention, with HE staining and oil red O staining adopted, the abdominal aortic morphology and peripheral lipid deposition were observed. Separately, using WST-1, TBA and micro-plate method, the superoxide dismutase (SOD) activity and the levels of malondialdehyde (MDA) and nitric oxide (NO) in the serum were detected. The protein expression of mTOR, HIF-1α and VEGF in abdominal aorta were measured by Western blot method. Compared with those in the normal group, the levels of TC, TG and LDL-C increased (P<0.01) and HDL-C decreased (P<0.01) in the serum of the rats in the model group, the moxibustion group and the inhibitor group after model establishment. When compared with the normal group after intervention, in the model group, the serum levels of TC, TG, LDL-C and MDA increased (P<0.01), HDL-C level, SOD activity and NO level were reduced (P<0.01); the cell structure of the abdominal arota was abnormal, the peripheral lipids deposited seriously; and the protein expression of mTOR, HIF-1α and VEGF of abdominal aorta was elevated (P<0.01, P<0.05). In comparison with the model group, the levels of TC, TG, LDL-C and MDA were reduced (P<0.01), HDL-C levels, SOD activities and NO levels elevated (P<0.01, P<0.05), as well as the protein expression of mTOR, HIF-1α and VEGF of abdominal aorta (P<0.01, P<0.05) in the moxibustion group and the inhibitor group; besides, the vascular structure was ameliorated and the lipid deposition reduced in the moxibustion group, while, the vascular structure was still abnormal and the lipid deposition declined in the inhibitor group. When compared with the inhibitor group, the serum SOD activity and NO level increased (P<0.05) and MDA decreased (P<0.05); and the protein expression of mTOR, HIF-1α and VEGF of abdominal aorta was elevated (P<0.01, P<0.05) in the moxibustion group. The vascular injury due to hyperlipidemia is repaired by moxibustion with wheat-grain size cone at "Zusanli" (ST 36) through ameliorating oxidative stress, which is associated potentially with the modulation of mTOR/HIF-1α/VEGF signaling pathway.

Abstract. Okokon JE, Onunkun JA, Anagboso MO, Udobang JA. 2024. Solanum anomalum leaf extract mitigated doxorubicin-induced kidney toxicity and oxidative stress in male rats. Asian J Nat Prod Biochem 22: 59-66. Solanum anomalum Thonn. ex Schumach (family Solanaceae) is a shrub whose leaves are used locally to treat various diseases. Evaluation of the antidotal activity of leaf extract of S. anomalum was carried out to ascertain its uses in traditional medicine. The leaf extract (70-210 mg/kg) of S. anomalum was investigated for nephroprotective activity against doxorubicin-induced kidney toxicity in rats. Kidney function parameters, kidney histology, and kidney oxidative stress markers were used to assess the kidney protective effect of the extract. The leaf extract (70-210 mg/kg) significantly (p&lt;0.05-0.01) reduced the levels of creatinine, urea, and electrolytes that were elevated by doxorubicin. Also, the MDA level elevated by doxorubicin was reduced by the extract co-administration, while the levels of GSH, GST, SOD, GPx, and CAT that were decreased by doxorubicin were significantly (p&lt;0.01) elevated by the leaf extract. Histology of the kidney sections of extract-treated animals showed reductions in the pathological features compared to the organotoxic-treated animals. The chemical pathological changes were consistent with histopathological observations, suggesting marked nephroprotective potential. The anti-toxic effect of this plant may, in part, be mediated through the plant's chemical constituents. S. anomalum possesses anti-toxicant properties that can be exploited in treating doxorubicin-related toxicities.

Objective: Cisplatin (DDP, cis-diamminedichloroplatinium II) is one of the most potent chemotherapeutic antitumor drugs, but is able to generate reactive oxygen species (ROS) and it also inhibits the activity of antioxidant enzymes in renal tissue. In the present study, we investigated the preventive effect of 100, 200 and 400 mg/kg b.w. doses of vitamin E (VE), and 25, 50, and 100 mg/kg b.w. doses of vitamin A (VA) combination on malondialdehyde (MDA), nitric oxide (NO), and glutathione (GSH) levels and superoxide dismutase (SOD) activity in cisplatin-induced toxicity in rat kidneys. Our literature survey indicated a lack of any experimental study showing the beneficial effect of VA on cisplatin-induced MDA, NO, GSH and SOD changes. For this reason, we hoped that this study would provide a unique contribution in that respect. Materials and Methods: 59 Wistar rats (11 to replace prematurely lost animals) were used. 48 evaluable rats were divided into 8 groups (n = 6 in each group): control group, DDP alone (5 mg/kg b.w.) group, 3 VE combination treatment groups of VE100+DDP, VE200+DDP, and VE400+DDP, and 3 VA combination treatment groups of VA25+DDP, VA50+DDP, and VA100+DDP. Kidney MDA, GSH, NO levels and SOD activities were determined for the assessment of oxidant-antioxidant balance. Results: While in the DDP group the tissue levels of MDA and NO were found to be significantly higher than in the control group, GSH levels and SOD activities were significantly lower. MDA and NO levels were found to be significantly lower and GSH levels and SOD activities significantly higher in the VE200+DDP and VE400+ DDP groups when compared with the DDP alone group. MDA and NO levels were found to be significantly lower in the VA50+DDP and VA100+DDP groups when compared with the DDP alone group. However, identical comparisons with the DDP alone group showed significantly higher GSH levels and SOD activities in the VA25+DDP, VA50+DDP, and VA100+DDP groups. Among the VE100+ DDP, VE200+DDP, and VE400+DDP groups, and VA25+ DDP, VA50+DDP, and VA100+DDP groups, MDA and NO levels decreased and GSH levels and SOD activities increased steadily and significantly as the doses of VE and VA increased. Conclusion: These vitamins would be effective in protecting against cisplatin-induced tissue damage in rat kidneys. It is possible that the toxic effect of cisplatin is somehow minimized by a compensatory mechanism involving VE and VA via induction of antioxidant enzyme activities following intraperitoneal injection of DDP.

Why should an angiogenic factor modulate tubular structure in diabetic nephropathy? Some answers, more questions

Effects of Increased Renal Tubular Vascular Endothelial Growth Factor (VEGF) on Fibrosis, Cyst Formation, and Glomerular Disease

To assess the roles of oxidative stress and vascular endothelial growth factor (VEGF) in pterygium pathogenesis and prevention of pterygium recurrence after surgical excision. Surgically removed pterygium tissue from 35 pterygium patients and normal conjunctival samples from 15 patients matched for age and sex (used as controls) constituted the study samples. The conjunctival samples were preserved at - 80 °C until analysis. Catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH) and total antioxidant (TAO) enzymatic activity and the levels of nitric oxide (NO), malondialdehyde (MDA) and VEGF were studied in both groups. To evaluate the recurrence rate after surgical excision, the pterygium patients were further subdivided into three groups according to the adjuvant therapy used to prevent recurrence. Group 1 consisted of 10 patients who were treated with 0.2 mg mitomycin-c (MMC) for 2 min. Group 2 consisted of 12 patients treated with subconjunctival bevacizumab injection after surgical removal of the pterygium. Group 3 consisted of 13 patients who underwent combined treatment with 0.2 mg of MMC for 2 min and subconjunctival bevacizumab injection. The follow-up of patients in the three groups ranged from 7 to 15 months. The activities of CAT, SOD, GSH and TAO were significantly lower in pterygium samples than in normal conjunctival samples (p < 0.0001 each). The levels of MDA (p = 0.046), NO (p < 0.0001) and VEGF (p < 0.0001) were significantly higher in pterygium patients than in controls. The lowest recurrence rate after surgical excision was that of the third group. Oxidative stress and VEGF could play a role in the pathogenesis of pterygium as indicated by decreased antioxidant enzymatic activity and increased levels of VEGF in the pterygium tissue and the role of MMC and anti-VEGF therapy in decreasing the recurrence rate after surgical excision.

Mercuric chloride was introduced per Os in albino rats (Rattus norvegicus) as per the LD50 (9.26 mg/kg b.w.). The assessment of mercuric chloride toxicity was done both after acute (0.926 mg/kg b.w.) and sub-acute (0.033 mg/kg b.w.) per Os treatment, while Panax ginseng was also introduced (10 mg/kg b.w.) per Os in the albino rats separately. Mercuric chloride treatment significantly increases mercury retention in liver and blood serum along with increase in liver weight, while Panax ginseng alone caused significant decrease in liver weight and mercury retention in liver and blood. Increase in mercury retention in blood serum and liver is due to the reactivity between –SH protein of blood serum and liver with oxidized form of mercury (Hg++), while decrease in Panax ginseng treatment is due to antioxidant activity of Panax ginseng the ginsenosides. Moreover, mercuric chloride followed by Panax ginseng and Panax ginseng followed by mercuric chloride treatment revealed significant modulation for raised mercury retention and liver weight towards normal level along with blood serum and liver changes. The results suggest a modulating role of Panax ginseng extract against raised mercury concentration in blood serum and liver under stress of mercuric chloride.

Physical exercise improves learning and memory abilities by increasing the levels of several growth factors in the hippocampus. One growth factor, vascular endothelial growth factor (VEGF), is primarily produced in the muscles and not only increases in the periphery during exercise but can also cross the blood-brain barrier. The aim of this study is to investigate the effects of regular aerobic chronic exercise on different types of muscle fibers and the relationships between learning/memory and muscle induced-VEGF. Following a one-week adaptation period, male rats underwent treadmill training at a speed of 8 m/min for 30 min daily, 3 days a week for 6 weeks. Memory functions were evaluated using the Morris water maze. VEGF, superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were measured in type 1 and type 2 muscle fibers and VEGF levels were also measured in the hippocampus. Exercise positively affected both learning and memory and also increased VEGF levels in both muscle fiber types. Muscle VEGF levels positively correlate with hippocampal learning and hippocampal VEGF levels. Exercise reduced both SOD and MDA levels in type 1 and type 2 muscle fibers, whereas GPx levels decreased only in type 2 muscle fibers. Our findings suggest that regular aerobic exercise elevates VEGF levels and diminishes oxidative stress in both fiber types. Exercise-induced VEGF levels in both type 1 and 2 muscle fibers appear to be associated with the positive effect of exercise on learning and memory function and is accompanied by an increase in VEGF levels in the hippocampus. Further research is needed to elucidate the exact mechanism by which fiber type-specific VEGF mediates hippocampal neurogenesis and angiogenesis. Physical exercise improves learning and memory abilities by increasing the levels of several growth factors in the hippocampus. One growth factor, vascular endothelial growth factor (VEGF), is primarily produced in the muscles and not only increases in the periphery during exercise but can also cross the blood-brain barrier. The aim of this study is to investigate the effects of regular aerobic chronic exercise on different types of muscle fibers and the relationships between learning/memory and muscle induced-VEGF. Following a one-week adaptation period, male rats underwent treadmill training at a speed of 8 m/min for 30 min daily, 3 days a week for 6 weeks. Memory functions were evaluated using the Morris water maze. VEGF, superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were measured in type 1 and type 2 muscle fibers and VEGF levels were also measured in the hippocampus. Exercise positively affected both learning and memory and also increased VEGF levels in both muscle fiber types. Muscle VEGF levels positively correlate with hippocampal learning and hippocampal VEGF levels. Exercise reduced both SOD and MDA levels in type 1 and type 2 muscle fibers, whereas GPx levels decreased only in type 2 muscle fibers. Our findings suggest that regular aerobic exercise elevates VEGF levels and diminishes oxidative stress in both fiber types. Exercise-induced VEGF levels in both type 1 and 2 muscle fibers appear to be associated with the positive effect of exercise on learning and memory function and is accompanied by an increase in VEGF levels in the hippocampus. Further research is needed to elucidate the exact mechanism by which fiber type-specific VEGF mediates hippocampal neurogenesis and angiogenesis.

Introduction: Mercury has hematotoxic, hepatotoxic, neurotoxic, nephrotoxic and genotoxic effects. Tissue damage induced by mercuric chloride (HgCl 2 ) is associated with the promotion of oxidative stress. In this study, Gallic acid (GA), as potent antioxidant compound, was examined against mercuric chloride (HgCl 2 )-induced kidney injury in Wistar rats. Methods and Results: In this experimental study, animals were divided into five groups (n=7). Groups 1 and 2 respectively received normal saline (2 ml/kg, orally.) and HgCl 2 (0.4 mg/kg, orally) for 28 consecutive days. Group 3 only received GA (200 mg/kg, orally) for 28 consecutive days. Groups 4 and 5 received orally GA at doses of 50 and 200 mg/kg, respectively, one hour after administration of HgCl 2 for 28 consecutive days. Then On the 29 th day, the rats were sacrificed, and blood samples were collected to determine biochemical parameters such as serum creatinine (Cr) and blood urea nitrogen (BUN) levels. For oxidative stress evaluation, malondialdehyde (MDA) and reduced glutathione (GSH) levels and also catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were evaluated in left kidney tissue. The right kidney was used for histological examination. The results obtained from our study showed a significant increase in the levels of MDA, Cr and BUN, and decrease of GSH, CAT and SOD after ingestion of HgCl 2 (p<0.05). Pre-treatment with GA showed diminished in the levels of MDA, Cr and BUN and enhanced of GSH, CAT, GPx and SOD activity ( p <0.05). Additionally the nephroprotective effect of the GA was established by the histological evaluation of the kidneys. Conclusions: Our results indicate that GA has protective effect against HgCl 2 -induced renal damage probably by scavenging free radicals, reducing the oxidative stress, and increasing the antioxidant defense mechanism. Key words: Nephrotoxicity, Mercuric chloride, Gallic acid, Rat. Grants: This work was supported in part by a research grant 94s124 from Ahvaz Jundishapur University of Medical Sciences, ahvaz, Iran.

Objective(s):Panax ginseng (PG) widely used for its various pharmacological activities, including effects on diabetes and its complications. This study aims to investigate the effect of PG on mortality-related hypomagnesemia, hyperlactatemia, metabolic acidosis, and other diabetes-induced abnormalities. Materials and Methods:Type 1 diabetes was induced by IV injection of alloxan monohydrate 110 mg/kg into New Zealand white rabbits weighing 2-2.5 kg. PG was supplied in drinking water for 20 weeks. The effects of the PG treatment on diabetes were evaluated through hematological and biochemical analysis including ELISA assays for insulin and glycated haemoglobin A1c (HBA1c) before and after PG extract was supplied. Results:The serum glucose, insulin, and HBA1c levels were significantly improved after the PG treatment compared to those found before PG treatment. In addition, Mg2+, lactate, and base deficit, and acidosis was significantly enhanced in treated rabbits. Moreover, PG showed hepato- and renoprotective effect. Likewise, electrolytes, lipid and protein profile were improved.Conclusion:The biochemical and hematological analysis data demonstrate that the PG is effective to alleviate the diabetes serious signs.

It has been shown that oxidative damage and inflammation caused by hyperglycemia in endothelial cells are key factors triggering diabetic vascular complications. The aim of the present study was to investigate the antioxidant and anti‑inflammatory effects of Danhong Huayu Koufuye (DHK)‑medicated serum on high glucose (HG)‑induced injury in endothelial cells, and examine its underlying mechanisms. EA. hy926 cells were treated with normal glucose, HG, or HG with DHK‑medicated serum. Cell viability was assessed using the MTT method. Apoptosis was detected using flow cytometry. Intracellular reactive oxygen species (ROS) levels were measured using the 2',7'‑dichlorodihydrofluorescein method. Cell culture supernatant was collected for detecting the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), and the levels of malondialdehyde (MDA). The protein expression levels of intercellular adhesion molecule‑1 (ICAM‑1), nuclear factor‑κB (NF‑κB), hypoxia‑inducible factor‑1α (HIF‑1α) and vascular endothelial growth factor (VEGF) were determined using western blot analysis. The results revealed that DHK‑medicated serum accelerated the proliferation and inhibited the apoptosis of cells treated with HG (P<0.01) in a dose‑dependent manner. Compared with the HG group, the high levels of ROS and MDA were significantly reduced by DHK‑medicated serum (P<0.01). A 10% concentration of DHK‑medicated serum increased the activities of SOD and GPx by 59.4 and 95.5%, respectively. The high protein expression levels of ICAM‑1, NF‑κB, VEGF and HIF‑1α were significantly ameliorated by DHK‑medicated serum (P<0.01, vs. HG group). These findings indicated that DHK‑medicated serum protected EA. hy926 cells from HG‑induced injury and apoptosis through antioxidation and anti‑inflammatory effects.

Vascular endothelial growth factor-C and -D are involved in lymphangiogenesis in mouse unilateral ureteral obstruction

This work aimed at investigating the potential modulatory effects and mechanisms of crocin against CCl4 -induced nephrotoxicity. Forty male rats were allocated for three weeks treatment with corn oil, CCl4 , crocin, or crocin plus CCl4 . Crocin effectively mitigated CCl4 -induced kidney injury as evidenced by amelioration of alterations in kidney histopathology, renal weight/100 g body weight ratio and kidney functions. Crocin modulated CCl4 -induced disturbance of kidney cytochrom-P450 subfamily 2E1 and glutathione-S-transferase. The attenuation of crocin to kidney injury was also associated with suppression of oxidative stress via reduction of lipid peroxides along with induction of renal glutathione content and enhancement of superoxide dismutase, glutathione peroxidase, and catalase activities. Crocin mitigated CCl4 -induced elevation of the renal levels of tumor necrosis factor-alpha, interleukin-6, prostaglandin E2, and active caspases-3. Collectively, crocin alleviated CCl4 -induced renal damage via modulation of kidney metabolizing enzymes, suppression of oxidative stress, inhibition of inflammatory cytokines, PGE2, and active caspase3 in kidney.

Evaluation of carotid intima-media thickness with vascular endothelial growth factor and malondialdehyde levels in patients with sarcoidosis.