Clinical and inflammatory response to antiviral treatments in dogs with parvoviral enteritis.

BACKGROUND: Canine parvoviral enteritis (CPE) is a fatal disease worldwide. The treatment of CPE is based mainly on supportive and symptomatic treatment. Antiviral addition to the treatment may result in a higher survival. OBJECTIVES: This study evaluated the effects of antiviral treatments with a standardized treatment (ST) on the clinical and inflammatory response of dogs with naturally occurring CPE. METHODS: Twenty-eight dogs with CPE caused by canine parvovirus type 2 were divided randomly into treatment groups. The ST group received fluid, antibiotic, antiemetic, and deworming treatments. The antiviral treatment groups received the same ST with an additional antiviral drug, recombinant feline interferon omega (rFeIFN-ω), oseltamivir (OSEL) or famciclovir (FAM). RESULTS: Compared to the healthy control, the tumor necrosis factor-α, interleukin-1ß, interferon (IFN)-α, IFN-γ, haptoglobin, and C-reactive protein values were high (p < 0.05) on day zero. At presentation, mild lymphopenia, neutropenia, and a high neutrophil to lymphocyte (LYM) ratio (NLR) were also observed. Adding rFeIFN-ω to the ST produced the best improvement in the clinical score with a decreased NLR, while leucocytes remained low and inflammatory markers stayed high on day three. The survival rates of the groups were 85.7% in ST+IFN, 71.4% in ST+OSEL, 71.4% in ST+FAM, and 57.1% in ST groups on day seven. CONCLUSIONS: Antiviral drugs may be valuable in treating CPE to improve the clinical signs and survival. In addition, the decrease in NLR in favor of LYM may be an indicator of the early prognosis before the improvement of leukocytes, cytokines, and acute phase proteins in CPE.

Silver Nanoparticles Loaded with Oleuropein Reduce Doxorubicin-Induced Testicular Damage by Regulating Endoplasmic Reticulum Stress, and Apoptosis.

Doxorubicin (DOX) is the most used chemotherapeutic agent for treating solid tumors. DOX treatment may lead to testicular damage using oxidative stress, resulting in infertility. These adverse effects may be prevented by the activation of antioxidant systems. Oleuropein (OLE) is a powerful flavonoid with several ameliorative effects, including antioxidative, antiproliferative, and anti-inflammatory. It would be more efficient and applicable in treating chronic human diseases if its poor bioavailability improves with a nano-delivery system. The current study aims to assess the histopathological changes and antioxidative effects of OLE loaded with silver nanoparticles oleuropein (OLE-AgNP) on the testicular injury triggered by DOX in rats. Forty-eight male albino rats were randomly divided into six groups as follows: the control, DOX (2.5 mg/kg), OLE (50 mg/kg), AgNP (100 mg/kg), OLE + AgNP (50 mg/kg), OLE (50 mg/kg) + DOX (2.5 mg/kg), AgNP (100 mg/kg) + DOX (2.5 mg/kg), and OLE-AgNP (50 mg/kg) + DOX (2.5 mg/kg) for 11 days. Oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress markers, sperm analysis, and histopathological analyses were performed on testicular tissues taken from rats decapitated after the applications and compared between the experimental groups. The tissue MDA level was lower in the OLE and OLE+AgNP-treated groups than in the DOX-treated group. In addition, SOD and GSH levels significantly increased in both the OLE and OLE+AgNP-treated groups compared to the DOX group. Both OLE and OLE+AgNP, particularly OLE+AgNP, ameliorated DOX-induced testicular tissue injury, as evidenced by reduced injury and improved seminiferous tubules and spermatocyte area. In addition, OLE and OLE+AgNP, especially OLE+AgNP, inhibited DOX-induced testicular tissue inflammation, apoptosis, and endoplasmic reticulum stress. The findings suggest that nanotechnology and the production of OLE+AgNP can ameliorate DOX-induced testicular damage.

The investigation of the effects of monosodium glutamate on healthy rats and rats with STZ-induced diabetes.

Monosodium glutamate (MSG, E621) is a flavor-enhancing food additive used widely in the food preparation industry and consumed regularly. It is considered that long-term consumption of MSG causes metabolic syndrome and obesity. Diabetes mellitus (DM) is a chronic metabolic disease characterized by high blood sugar, polyuria, polydipsia, and polyphagia, in which insulin secreted from pancreatic ß cells is inadequate for maintaining blood glucose homeostasis. Rats were application 65 mg/kg streptozotocin (STZ) solution intraperitoneally and a diabetes model was created. For this purpose, freshly prepared STZ was injected into the peritoneum. Tumor necrosis factor-α, interleukin (IL)-10, IL-6, and IL-1ß levels in STZ, MSG, and STZ + MSG groups were found to be significantly increased in inflammation parameters measured on the 28th day of administration when compared to the Control Group (p < 0.001). Also, although malondialdehyde (MDA) levels increased significantly in the STZ + MSG group when compared to the control group (p < 0.001), glutathione (GSH), and superoxide dismutase (SOD) levels were significantly decreased in the STZ, MSG, and STZ + MSG groups when compared to the control group (p < 0.001). Also, although glucose levels increased significantly in STZ and STZ + MSG at the end of the 28th day (p < 0.01), insulin levels decreased in STZ, MSG, and STZ + MSG groups when compared to the control groups (p < 0.01). As a result, it was found that STZ and MSG application significantly increased cytokine production, increased MDA, which is an oxidant parameter in pancreatic tissue, and decreased antioxidants (GSH and SOD) when compared to the control groups. It was also found that MSG disrupted the normal histological structure in pancreatic cells, and the damage was much more in both exocrine and endocrine pancreatic areas in the STZ + MSG group when compared to the STZ and MSG groups. It was considered that with the increased use of MSG, the susceptibility to DM might increase along with tissue damage significantly in diabetic groups, therefore, MSG must be used in a limited and controlled manner.

Citrate-coated silver nanoparticles loaded with agomelatine provide neuronal therapy in acute cerebral ischemia/reperfusion of rats by inhibiting the oxidative stress, endoplasmic reticulum stress, and P2X7 receptor-mediated inflammasome.

Cerebral ischemia and reperfusion are related to various situations like injuries after various traumas, oxidative stress, increased calcium ion, capillary hypoperfusion, microvascular hyperpermeability, leukocyte infiltration, and blood-brain barrier disruption. An antidepressant Agomelatine which is a melatonin receptor (MT1/MT2) agonist and serotonin receptor (5-HT2C) antagonist has been reported by studies to have antioxidant and anti-inflammatory effects. In our study, we aimed to detect the effects of citrate-coated silver nanoparticle-loaded agomelatine application on neurodegeneration, endoplasmic reticulum stress, autophagic and apoptotic cell death, inflammation, and P2X7R expression in the cerebral ischemia-reperfusion model to facilitate the passage of blood-brain barrier. Forty two Sprague-Dawley rats in total were divided into six equal groups (n:7) and applications were performed. Acute cerebral injury in the ischemia-reperfusion model was created 2 h after internal carotid artery ligation in rats and then at the 2nd hour of reperfusion citrate-coated silver nanoparticles loaded with Agomelatine were applied. Twenty four hours later, neurologic analysis on animals in experimental groups was performed, animals were decapitated and GSH, GPx, SOD, CAT, MDA, IL-1ß, and TNF-α parameters were examined after taking blood and the cerebral tissue samples. As a result, it was determined that ischemia-reperfusion caused endoplasmic reticulum stress in the cerebral tissues and thus caused cellular injury.

Blockade of P2X7 receptor-mediated purinergic signaling with A438079 protects against LPS-induced liver injury in rats.

The study aimed to investigate the hepatoprotective effects of purinergic receptor (P2X7R) antagonism by A438079 in liver damage. An experimental model of inflammation was performed by intraperitoneal (i.p.) lipopolysaccharide (LPS) administration in the rat. The groups were Control, A438079, dimethyl sulfoxide (DMSO), LPS, LPS + DMSO, and LPS + A438079. Following LPS (8 mg/kg) injection, A438079 (15 mg/kg) and DMSO (0.1 mL) were administrated (i.p) in the study groups. The blood and the liver tissues were removed for histological, biochemical, and western blot analyses. In the biochemical analysis, serum aspartate transaminase (AST) and alanine transaminase (ALT) concentrations, the tissue glutathione (GSH) level, and superoxide dismutase (SOD) activity dramatically decreased and malondialdehyde (MDA) level increased in the LPS and LPS + DMSO groups compared to the LPS + A438079 group. In the histological analysis, severe sinusoidal dilatation, necrotic hepatocytes, and inflammatory cell infiltration were observed in the LPS and LPS + DMSO groups while these effects were lessened in the LPS + A438079 group. The relative protein expression levels of P2X7R, Nf-kB-p65, IL-6, and Caspase-3 were significantly higher in the LPS and the LPS + DMSO groups than in the LPS + A438079 group. On the other hand, these protein expressions were considerably lower in the Control, A438079, and DMSO groups compared to the LPS + A438079 group. In addition, Bcl-2 protein expression was significantly lower in the LPS and the LPS + DMSO groups and higher in the LPS + A438079 group compared to the other groups. The protective effect of A438079 against LPS-induced hepatic inflammation may be related to P2X7R antagonism, inflammatory mediators, and apoptotic cell death.

Effects of dietary thyme and rosemary essential oils on biochemical parameters, anti-oxidant metabolism, small intestinal morphology and myofiber structure of superficial pectoral and biceps femoris muscles in broilers.

This study was aimed at determining the effects of dietary supplementation with thyme essential oil (TEO) and rosemary essential oil (REO) on blood parameters, the anti-oxidant metabolism in the liver, breast and drumstick muscle tissues, the morphology of the small intestine, and the myofibril structure of the superficial pectoral and biceps femoris muscles. For this purpose, 400 three-day-old male Ross 308 chicks were used. Five groups, each comprising 80 broilers, were established. The control group was fed on a basal diet alone and groups thyme-1, thyme-2, rosemary-1 and rosemary-2 received basal diets supplemented with 0.15 g kg-1 of TEO, 0.30 g kg-1 of TEO, 0.10 g kg-1 of REO and 0.20 g kg-1 of REO, respectively. The serum total cholesterol and low-density lipoprotein levels were decreased significantly in group thyme-1. Dietary TEO and REO significantly increased glutathione levels in all tissues. Drumstick catalase activity was significantly increased in groups thyme-1, thyme-2 and rosemary-2. Superoxide dismutase activity was significantly increased in the breast muscle of all groups that received dietary TEO and REO. Histomorphometrical analyses demonstrated that dietary supplementation with TEO and REO increased both crypt depth and villus height in the small intestine. In result, the tested doses of dietary TEO and REO were ascertained to improve the intestinal morphology and to increase the anti-oxidant metabolism mainly in the breast muscle, the drumstick muscle and liver.

P2X7 receptor antagonist A-438079 alleviates oxidative stress of lung in LPS-induced septic rats.

Sepsis is a deadly systemic inflammatory response of the body against infection resulting in immune response, cell differentiation and organ damage. Endotoxemia is one of the causes of sepsis-related acute respiratory distress and respiratory burst is an important generator of oxidants. Inflammation may be aggravated by overexpression of ATP-gated purinergic receptors (i.e., P2X7R) following cell damage. We aimed to evaluate the effects of P2X7R antagonist A-438079 on lung oxidative status and the receptor expression in endotoxemia of sepsis. Rats were subjected to sepsis by E. coli lipopolysaccharide (LPS) and treated with 15 mg/kg A-438079. The increase in circulatory IL-1ß and IL-8 concentrations in LPS group confirmed the systemic inflammatory response to endotoxemia compared with Control groups (p < 0.001). Besides, there was an increase in P2X7R expression in lung tissue after LPS administration. Compared with Control groups, there were significant increases in the values of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) (p < 0.001), and myeloperoxidase (MPO) (p < 0.05) in lung tissue of LPS group. P2X7R expression in lung and IL-1ß level in blood did not increase in LPS + A-438079 group. A-438079 decreased the lung levels of MDA, GSH, CAT and SOD (p < 0.001), and MPO (p < 0.01) in septic rats. As a result, administration of pathogen-associated LPS led to increased P2X7R expression into lung tissue and elevated lipid peroxidation product MDA with regard to oxidative damage. The P2X7R antagonist A-438079 alleviated the oxidative stress of lung with a balance of tissue oxidant/antioxidant factors in experimental sepsis in rats.

The protective effect of quercetin on cyclophosphamide-Induced lung toxicity in rats.

Cyclophosphamide (CYP) is an anticancer agent widely used in chemotherapy. It has been suggested that CYP causes toxicity in many organs, including the lungs and testes. Many studies have indicated that some antioxidants have possible protective effects against CYP's side effects. This study aimed to investigate the protective effect of quercetin (QUE) on CYP-induced lung toxicity in rats using histologic and biochemical methods. In the study, 50 male Sprague-Dawley rats weighing 220-250g were used. There were 4 experimental groups and 1 control group. Group I is the control group, which was given only intragastric (i.g.) solvent (corn oil) for 7days. Group II was given i.g. corn oil for 7days as a placebo, and a single dose of intraperitoneal (i.p.) CYP (200mg/kg) was given on day 7. Groups III and IV, respectively, were given QUE in doses of 50 and 100mg/kg, dissolved in corn oil, and administered i.g. for 7days. In addition, a single dose of CYP (200mg/kg, i.p.) was administered on the 7th day of study. In Group V, a 100mg/kg dose of QUE was given to rats i.g. for 7days. On the 8th day of the experiment, all groups of rats' blood and lung tissue samples were collected for analysis of oxidative stress parameters and histopathological examinations. In the biochemical result (although oxidative parameters were increased in favor of tissue damage) QUE administration revealed attenuated CYP toxicity in the rats 'lungs. In histologic analysis, QUE prevented the CYP-mediated tissue damage and the increase in mast-cell densities in the rats' lung tissues. The results of the present study have revealed that QUE provides a possible protective effect by inhibiting ROS and mast cell degranulation in induced lung damage.

Influences of Fucoxanthin on Alveolar Bone Resorption in Induced Periodontitis in Rat Molars.

The aim of this study was to evaluate the effects of systemic fucoxanthin treatment on alveolar bone resorption in rats with periodontitis. Thirty rats were divided into control, experimental periodontitis (EP), and experimental periodontitis-fucoxanthin (EP-FUCO) groups. Periodontitis was induced by ligature for four weeks. After removal of the ligature, the rats in the EP-FUCO group were treated with a single dose of fucoxanthin (200 mg/kg bw) per day for 28 consecutive days. At the end of the study, all of the rats were euthanized and intracardiac blood and mandible tissue samples were obtained for biochemical, immunohistochemical, and histometric analyses. Fucoxanthin treatment resulted in a slight decrease in tumor necrosis factor-α, interleukin-1ß, and interleukin-6 levels and a significant decrease in oxidative stress index. It was observed that fucoxanthin caused a significant reduction in receptor activator of nuclear factor kappa-ß ligand (RANKL) levels and a statistically non-significant elevation in osteoprotegerin and bone-alkaline phosphatase levels. There were no significant differences in alveolar bone loss levels between the EP and EP-FUCO groups. This experimental study revealed that fucoxanthin provides a limited reduction in alveolar bone resorption in rats with periodontitis. One of the mechanisms underlying the mentioned limited effect might be related to the ability of fucoxanthin to inhibit oxidative stress-related RANKL-mediated osteoclastogenesis.

Effect of agomelatine on adult hippocampus apoptosis and neurogenesis using the stress model of rats.

Agomelatine (AG) is an agonist of melatonin receptors and an antagonist of the 5-HT2C-receptor subtype. The chronobiotic properties of AG are of significant interest due to the disorganization of internal rhythms, which might play a role in the pathophysiology of depression. The present study was designed to assess the effects of the antidepressant-like activity of AG, a new antidepressant drug, on adult neurogenesis and apoptosis using stress-exposed rat brains. Over the period of 1 week, the rats were exposed to light stress twice a day for 1h. After a period of 1 week, the rats were given AG treatment at a dose of either 10mg/kg or 40mg/kg for 15 days. The animals were then scarified, and the obtained tissue sections were stained with immuno-histochemical anti-BrdU, Caspase-3, and Bcl-2 antibodies. Serum brain-derived neurotrophic factor (BDNF) concentrations were measured biochemically using a BDNF Elisa kit. Biochemical BDNF analysis revealed a high concentration of BDNF in the serum of the stress-exposed group, but the concentrations of BDNF were much lower those of the AG-treated groups. Immuno-histochemical analysis revealed that AG treatment decreased the BrdU-positive and Bcl-2-positive cell densities and increased the Caspase-3-positive cell density in the hippocampus of stress-induced rats as compared to those of the stress group. The results of the study demonstrated that AG treatment ameliorated the hippocampal apoptotic cells and increased hippocampal neurogenesis. These results also strengthen the possible relationship between depression and adult neurogenesis, which must be studied further.

Effects of Melatonin on Oxidative Stress Index and Alveolar Bone Loss in Diabetic Rats With Periodontitis.

BACKGROUND: The aim of this study is to evaluate the effects of systemic melatonin treatment on serum oxidative stress index (OSI) and alveolar bone loss (ABL) in rats with diabetes mellitus (DM) and periodontitis. METHODS: Seventy Sprague Dawley rats were divided into control, experimentally induced periodontitis (EP), DM, EP-DM, EP and melatonin treatment (EP-MEL), DM and melatonin treatment (DMMEL), and EP-DM-MEL groups. DM was induced by alloxan, after which periodontitis was induced by ligature for 4 weeks. After removal of the ligature, the rats in the melatonin groups (EP-MEL, DM-MEL, and EP-DM-MEL) were treated with a single dose of melatonin (10 mg/body weight) every day for 14 consecutive days. At the end of the study, all of the rats were euthanized, and intracardiac blood samples and mandible tissues were obtained for biochemical and histologic analyses. Serum levels of total oxidant status/total antioxidant status and OSI were measured. In addition, neutrophil and osteoclast densities and myeloperoxidase activities were determined in gingival tissue homogenates, and ABL was evaluated with histometric measurements. RESULTS: Melatonin treatment significantly reduced fasting plasma glucose levels in the rats with DM. In addition, reduced OSI and ABL levels were detected in the EP-MEL and DM-MEL groups; the reductions in the EP-DM-MEL group were found to be more prominent. Melatonin also significantly decreased the increased myeloperoxidase activities and osteoclast and neutrophil densities in the EP, DM, and EP-DM groups. CONCLUSION: It is revealed in this experimental study that melatonin significantly inhibited hyperglycemia-induced oxidative stress and ABL through antiDM and antioxidant effects in rats with DM and periodontitis.

Therapeutic Effects of Melatonin On Liver And Kidney Damages In Intensive Exercise Model of Rats.

Extensive exercise induces inflammatory reactions together with high production of free radicals and subsequent liver and kidney tissues damage. This study was designed to investigate for effects of melatonin on liver and kidney tissues in the extensive exercise exposed rats and non-exercised rats. In this research, 24-male Sprague-Dawley rats were divided into four groups. For exercise rat model, the rats were exposed to slow pace running with the velocity of 10 m/min for 5 minutes for five days just before the study. And for last ten days after adaptation period, the exercise was improved as 15 min with the speed of 20 m/min and intra-peritoneal melatonin injection has been performed to the melatonin treated groups with the dose of 10 mg/kg. Biochemical results revealed a decrease in the parameters of kidney and liver enzymes in exercise-group and an increase in the parameters of serum, liver and kidney enzymes in the group that melatonin-exercise-group. As for histological analysis, while it is observed that there are cellular degenerations in the liver and kidney tissues with exercise application, a decrease has been observed in these degenerations in the group that melatonin was applied. At the end of the research, it has been determined that exercise application causes some damages on liver and kidney, and these damages were ameliorated with melatonin treatment.

Therapeutic Effects of Melatonin on Alveolar Bone Resorption After Experimental Periodontitis in Rats: A Biochemical and Immunohistochemical Study.

BACKGROUND: The present study aims to investigate the effects of systemic melatonin administration on alveolar bone resorption in experimental periodontitis in rats. METHODS: Twenty-four male Sprague-Dawley rats were divided into three groups (control, experimental periodontitis [Ped], and experimental periodontitis treated with melatonin [Mel-Ped]). For periodontitis induction, first molars were ligatured submarginally for 4 weeks. After ligature removal, rats in the Mel-Ped group were treated with a daily single dose of 10 mg/kg body weight melatonin for 15 consecutive days. At the end of the study, intracardiac blood samples and mandible tissues were obtained for histologic, biochemical, and radiographic analysis. Serum markers related to bone turnover, calcium, phosphorus, bone alkaline phosphatase (b-ALP), and terminal C telopeptide of collagen Type I (CTX) were analyzed. Myeloperoxidase levels were determined in gingival tissue homogenates, and receptor activator of nuclear factor-kappa B ligand (RANKL) activation was analyzed in the mandible samples stereologically. Alveolar bone loss was also evaluated radiographically in the mandible samples of each group. RESULTS: Melatonin treatment decreased serum CTX levels and increased b-ALP levels. Serum calcium and phosphorus levels were not statistically different among groups (P >0.05). Alveolar bone resorption and myeloperoxidase activity were statistically higher in the Ped group compared to the Mel-Ped group (P <0.05). Immunohistochemical staining of RANKL and osteoclast activity were significantly lower in the Mel-Ped group compared to the Ped group (P <0.05). CONCLUSION: This study reveals that melatonin treatment significantly inhibits regional alveolar bone resorption and contributes to periodontal healing in an experimental periodontitis rat model.

The role of carnitine on ovariectomy and inflammation-induced osteoporosis in rats.

This study was carried out to assess the protective bone-sparing effect of carnitine with anti-inflammatory properties on chronic inflammation-induced bone loss in ovariectomised (OVX) rats. A total of 64 rats were divided into eight groups. Sixteen rats were sham-operated (SH) while the others were ovariectomised (OVX). (1) SH, (2) sham + inflammation (SHinf), (3) OVX, (4) ovariectomy + inflammation (OVXinf), (5) OVX + CAR1, (6) OVX + CAR2, (7) OVXinf + CAR1, (8) OVXinf + CAR2. After the ovariectomy surgery, all the groups (3, 4, 5, 6, 7, and 8) were allowed to recover for two months. Sixty days after the OVX, inflammation was induced by subcutaneous injections of talc in groups 2, 4, 7, and 8. Group 5 and 7 were given 50 mg/kg CAR; Group 6 and 8 were given 100 mg/kg CAR from the 60th to the 80th day. Serum levels of TNF-α, IL-1, IL-6, OP, and OC were assessed to determine inflammation and to evaluate osteoblastic activity. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry in femur bones of rats. Carnitine administration was able to restore BMD up to values measured in both the OVX and the SH animals. The serum levels of TNF-α, IL-1ß, and IL-6 were increased significantly in the OVXinf rats compared with the SH group. In OVX rats, inflammation which is evaluated by serum cytokine levels exacerbated this bone loss, as supported by values of BMD of the total femur. The two different doses of carnitine reduced bone loss and improved inflammatory biomarkers.

Immune modulatory and antioxidant effects of melatonin in experimental periodontitis in rats.

Melatonin is an important antioxidant, and through its anti-inflammatory effects it can control immune responses, oxidative stress, and defense cell infiltration. Periodontitis is a disease of the oral cavity and the generation of free radicals is an important consideration in this disease. Therefore, we examined the immune-modulatory and antioxidant roles of melatonin in the treatment of periodontitis. In all, 30 male Wistar rats were randomly divided into three groups: the control group, the periodontitis-induced (PED) group, and the periodontitis+melatonin treatment (MEL+PED) group. The control group received no treatment, whereas periodontitis was induced in both the PED and the MEL+PED groups, with the MEL+PED group being treated with systemic melatonin. For the periodontitis-induced groups, the rats' mandibular first molar teeth were ligatured (3-0 cotton) in a submarginal position for 4 weeks, and then the ligature was removed. After removal of the ligature, melatonin was administered only to the MEL+PED group (an ip dose of 10mg/kg body wt for 15 days at 11:00 PM each day). In the histological examination, the MEL+PED group, which received the melatonin, showed reduced inflammatory cytokines (IL-1ß, from 97.47 to 84.24pg/ml; TNF-α, from 0.22530 to 0.22519pg/ml), regulated oxidative stress parameters (MDA, from 41,458 to 30,708nmol/g; GSH, from 18,166 to 25,858nmol/mg), and less periodontal tissue destruction (CEJ-PL, lingual, from 244.54 to 140.57µm; buccal, from 235.6 to 158.93µm; and CEJ-BC, lingual, from 383.65 to 287.76µm; buccal, from 391.92 to 296.12µm). From these findings we conclude that, even when periodontitis was induced, melatonin reduced the oxidative damage in the rats' periodontal tissue by inhibiting the inflammatory effects and by restoring the antioxidants.

Antioxidant vitamins in atherosclerosis--animal experiments and clinical studies.

Atherosclerotic heart diseases are universal problems in modern society. Oxidative damage to lipids is a primary cause of atherosclerosis. There are many choices for treatment, but no definite recommendations to prevent the occurrence of the disease. There is a relationship between atherosclerotic risk factors and increased vascular production of reactive oxygen species (ROS). Oxidized low-density lipoproteins (LDL) and ROS may directly cause endothelial dysfunction by reducing endothelial nitric oxide (NO) bioavailability. Vitamin E can to some degree prevent the consequences of oxidized LDL, and vitamin C provides NO synthase activity. Although prolonged use of vitamin A, C, and E supplementation in pharmaceutical forms has been proven to be effective in preventing atherosclerosis in animal experiments, this has not yet been demonstrated in clinical trials with human beings. It should be taken into account that the evidence has been gathered from young/adult experimental animals with early stages of arthrosclerosis and from in-vitro studies, while most of the clinical trials have involved older patients with late stages of the disease. Prolonged use of vitamins in the diet has not yet been recommended in human beings. There is some indication that a diet rich in antioxidant fruit and vegetables may be beneficial in the prevention of cardiovascular events.

Protective effect of Panax ginseng against serum biochemical changes and apoptosis in kidney of rats treated with gentamicin sulphate.

The protective effects of Panax ginseng (PG) on gentamicin sulphate (GS) induced acute nephrotoxicity were investigated in rats. A total of 32 adult Sprague-Dawley rats were randomly divided into 4 equal groups and treated by intraperitoneous route for 10 days with: 0.5 mL of isotonic saline (group C), GS 100 mg/kg/day (group GS), co treatment PG (100 and 200 mg/kg/day) plus GS (100 mg/kg/day). After the last injection, kidney markers (urea, creatinine and blood urea nitrogen-BUN) and hepatic markers (aspartate aminotransferase-AST, alanine aminotransferase-ALT, gama glutamil transferase-GGT), and biochemical parameters were analyzed using diagnostic kits. Also, kidney changes were evaluated by immunohistochemical and stereological methods. GS treatment induced significant elevation (P < 0.05) in kidney and hepatic markers, most of biochemical parameters, and Bax immunoreactivity as well. However, co treatments with both doses of PG (100 and 200 mg/kg/day) significantly alleviated (P < 0.05) the GS-induced elevations and have partially protected rats from nephrotoxicity (reduction of kidney damage, and of urea, creatinine and BUN concentrations, and of apoptotic index). Both biochemical results and immunohistochemical evidence showed that administration of PG reduced the gentamicin-induced nephrotoxicity.