Effects of boric acid on ovarian tissue damage caused by experimental ischemia/reperfusion.

We investigated the role of boric acid (BA) in ovarian tissue damage caused by ischemia/reperfusion (I/R) in the rat. We established four groups of seven adult female rats: untreated control; ovarian I/R; 15 mg/kg BA; I/R + 15 mg/kg BA. Ovarian levels of lipid peroxidase (LPO), myeloperoxidase (MPO), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and interleukin-6 (IL-6) were measured biochemically. Ovaries were evaluated for histopathology and investigated using immunohistochemistry. We detected greater LPO activity and less CAT, SOD and GSH levels in the I/R groups compared to the control group. LPO and MPO levels in ovarian samples for the I/R goup were increased significantly compared to untreated controls. The levels of LPO and MPO in ovarian tissue for the I/R + BA group were not significantly different from controls. SOD and GSH activity in ovarian tissue was increased significantly compared to controls. We found degenerated parenchymal cells, hemorrhage, necrotic parenchyma cells and congestion in the I/R groups. Expression of 8-OHdG was greater in the I/R group than in controls. Although immunostained cells were dense in the ovarian tissue in the I/R group, the number of immunostained cells was decreased by application of BA to the I/R group. BA exhibits a protective effect on ovarian tissue against I/R damage in the rat.

Gastroprotective effects of oleuropein and thymol on indomethacin-induced gastric ulcer in Sprague-Dawley rats.

Ethnopharmacological studies demonstrated that thymol (Thym) and oleuropein (Ole) have therapeutic potential for gastric ulcers. The molecular mechanism underlying the gastroprotective effects of these compounds have not been elucidated yet especially for their individual and combination use at high dose. Therefore, this study was conducted to explore their gastroprotective mechanisms on indomethacin (Indo)-induced gastric ulcer model. Ole (50,100, 250, and 500 mg/kg) and Thym (50,100, 200, and 500 mg/kg) were orally administered to the rats 10 min before the induction of ulcer with Indo. The combination of 500 mg/kg doses of Ole and Thym were applied. The gastric mucosa was evaluated histopathologically. Moreover, TAC/TOS, tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), endothelial nitric oxide synthase (eNOS), and caspase-3 levels were assessed by ELISA and the caspase-3 and TNF-α expressions were quantified by qRT-PCR. Indo-induced histopathological changes while Ole and Thym pretreatment prevented these effects. Unlike the 500 mg/kg dose of Ole treatment, the 500 mg/kg dose of Thym administration enhanced these damages. The decreased TAC, PGE2 levels and increased TOS, eNOS, TNF-α, caspase-3 levels were obtained in Indo group. However, these changes were reversed by Ole and Thym groups except the 500 mg/kg dose of Thym and the combination treatment groups. Similar trends were observed in the caspase-3 and TNF-α expression levels. These results demonstrated that enhanced inflammation, oxidant/antioxidant imbalance, and apoptotic activities were occurred in Indo, 500 mg/kg dose of Thym and the combination treatment groups while not in the other groups. The findings demonstrated the gastroprotective ability of Ole and low doses of Thym in gastric ulcer models.

The propolis and boric acid can be highly suitable, alone/or as a combinatory approach on ovary ischemia-reperfusion injury.

PURPOSE: Ovarian ischemia-reperfusion (IR) damage continues to be a serious infertility problem. The oxidative stress plays central role in the development of IR injuries. Activation of antioxidants decreases IR injuries; however, the efficacy of antioxidant agents remains controversial. Unfortunately, there has been no evidence for medicinal use of boric acid (BA) and propolis (Prop) on ovarian IR injury on rats so far. This study will provide to reveal the potential applications of the Prop and BA in ovarian IR therapy. METHODS: The Sprague-Dawley rats were randomized into five groups: I-control, II-IR, 3 h of ischemia and 3 h of reperfusion, III and IV-a signal dose of oral BA (7 mg/kg) and Prop (100 mg/kg) alone 1 h before induction of IR, V-Prop and BA together 1 h before induction of IR. SOD (superoxide dismutase), CAT (catalase), GSH (glutathione), MPO (myeloperoxidase), MDA (malondialdehyde), and IL-6 (interleukin-6) levels were quantified by ELISA and the TNF-α (tumor necrosis factor-α), 8-OHdG (8-hydroxylo-2'-deoxyguanosin) and Caspase-3 expressions were performed by immunohistochemical analyses. RESULTS: BA and Prop pretreatment significantly reduced MPO, MDA, and IL-6 levels and pathologic score in IR rats, with no effects in control group. These agents used in therapy also decreased TNF-α, 8-OHdG and Caspase-3 protein expressions increased by IR. Furthermore, BA and Prop combination showed significant ameliorative effects on ovary injury caused by IR through acting as an antioxidant, anti-inflammatory and antiapoptotic agent. CONCLUSION: BA and Prop alone and especially in combination could be developed as therapeutic agents against ovary IR injury.

Propolis and Its Combination with Boric Acid Protect Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Inhibiting Oxidative Stress, Inflammation, DNA Damage, and Apoptosis in Rats.

Ischemia reperfusion (I/R) injury which causes kidney dysfunction is one of the most studied diseases directly linked to oxidative stress. In this regard, it is important to protect cells against damage by inducing antioxidant response. Herein, we aimed to evaluate the therapeutic roles and possible mechanisms of propolis and boric acid in kidney I/R injury based on relevant basic research and clinical studies. Sprague-Dawley rats were subjected to 50 min of ischemia followed by 3 h of reperfusion. Animals were randomly divided into a control group (the abdominal wall was just opened and closed), an I/R injury group, the propolis intervention group (200 mg/kg, intragastric administration, 1 h before ischemia), boric acid intervention group (14 mg/kg, intragastric administration 1 h before ischemia), and the propolis + boric acid intervention group (intragastric administration 1 h before ischemia). Kidney function, the antioxidant defensive system, and renal damage were assessed. In addition, the oxidative stress and inflammatory status were estimated in renal tissue. Furthermore, DNA damageand apoptosis were detected by immunohistochemistry. When compared with I/R group, propolis alone and especially propolis + boric acid groups significantly improved functional parameters. While the antioxidant response was increased, renal injury size and apoptosis were significantly decreased in both groups. Also, the MDA and TNF-α levels besides the 8-OHdG formation were downregulated. According to these outcomes, it can be said that especially propolis together with boric acid ameliorates kidney injury caused by I/R through acting as an antioxidant, anti-inflammatory, and antiapoptotic agent. In conclusion, propolis alone and its combination with boric acid could be developed as therapeutic agents against serious renal I/R injuries.

Effect of oleuropein against chemotherapy drug-induced histological changes, oxidative stress, and DNA damages in rat kidney injury.

Cisplatin-based chemotherapy is responsible for a large number of renal failures, and it is still associated with high rates of mortality today. Oleuropein (OLE) presents a plethora of pharmacological beneficial properties. In this study we investigated whether OLE could provide sufficient protection against cisplatin-induced nephrotoxicity. With this aim, Sprague-Dawley rats were divided into eight groups: control; 7 mg/kg/d cisplatin, 50 mg/kg, 100 mg/kg, and 200 mg/kg OLE; and treatment with OLE for 3 days starting at 24 hours following cisplatin injection. After exposure to the chemotherapy agent and OLE, oxidative DNA damage was quantitated in the renal tissue of experimental animals by measuring the amount of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adducts. Malondialdehyde (MDA) level, total oxidative stress (TOS), and total antioxidant status (TAS) were assessed to determine the oxidative injury in kidney cells. The histology of the kidney was examined using four different staining methods: hematoxylin-eosin (H&E), periodic acid Schiff (PAS), Masson trichrome, and amyloid. In addition, the blood urea nitrogen (BUN), uric acid (UA), and creatinine (CRE) levels were established. Our experimental data showed that tissue 8-OHdG levels were significantly higher in the cisplatin group when compared to the control group. The glomerular cells were sensitive to cisplatin as tubular cells. In addition, treatment with cisplatin elevated the levels of BUN, UA, CRE, and TOS, but lowered the level of TAS compared to the control group. The OLE therapy modulated oxidative stress in order to restore normal kidney function and reduced the formation of 8-OHdG induced by cisplatin. Furthermore, the OLE treatment significantly reduced pathological findings in renal tissue. We demonstrate for the first time that OLE presents significant cytoprotective properties against cisplatin-induced genotoxicity by restoring the antioxidant system of the renal tissue. According to our findings, OLE is a promising novel natural source for the prevention of serious kidney damage in current chemotherapies.

Oleuropein Ameliorates Cisplatin-induced Hematological Damages Via Restraining Oxidative Stress and DNA Injury.

The prevalence of cancer, in the world is increasing steadily. Despite intense research efforts, no approved therapy is yet available. Cisplatin is a chemotherapeutic drug but induces acute tissue injury. Oleuropein (OLE) is a major phenolic compound and used as a possible natural antioxidant, antimicrobial, and anticancer agent. We hypothesized that antioxidant activity of OLE may decrease cisplatin-induced oxidative stress and prevent to the development of chemotherapeutic complications including abnormality in hematological condition. Male Sprague Dawley rats were used in the experiments. Rats were randomly assigned to one of eight groups: control group; group treated with i.p. injection in a single dose of 7 mg/kg/day cisplatin; groups treated with 50, 100 and 200 mg/kg/day OLE (i.p.); and groups treated with OLE for 3 days starting at 24 h following cisplatin injection. First, hematological assessment was appreciated between control and experimental groups. Second, total oxidative stress (TOS) and total antioxidant capacity (TAC) levels of blood were measured by biochemical studies. In addition to this, oxidative DNA damage was determined by measuring as increases in 8-hydroxy-deoxyguanosine (8-OH-dG) adducts. The treatment with cisplatin elevated the TOS and 8-OH-dG levels that were then reversed by OLE. Reductions in antioxidant capacity with respect to corresponding controls were also restored by OLE treatment. These findings suggest that the OLE treatment against cisplatin-induced toxicity improves the function of blood cells and helps them to survive in the belligerent environment created by free radicals.

Impact of high-dose oleuropein on cisplatin-induced oxidative stress, genotoxicity and pathological changes in rat stomach and lung.

The current systemic treatments of the various solid tumors involve Cisplatin (CIS)-based chemotherapy. Due to its cytotoxicity, this approach is limited. Moreover, the safety of CIS is only discussed especially in breast and stomach cancers. Therefore, we, for the first time, explored the restorative efficacy of oleuropein (OLE), in stomach and lung injuries induced by CIS. Sprague-Dawley rats were divided into eight groups: control CIS, OLE and CIS + OLE. Single dose of (7 mg/kg) CIS was administered intraperitoneally to CIS and CIS + OLE groups. After 24 h, 50, 100 and 200 mg/kg OLE was given for three consecutive days to OLE and CIS + OLE groups. The 8-OH-dG, total oxidative/antioxidant status (TOS/TAS) and malondialdehyde (MDA) levels were evaluated and histopathological analyses were performed on the studied tissues. The results indicated that CIS significantly increased 8-OH-dG, MDA and TOS levels and caused severe tissue damages. However, high dose of OLE induced a significant decrease in the 8-OH-dG, MDA levels, an increase in TAS levels and it restores CIS-induced tissue damages. We hope that the results of this study will provide an impetus for future studies on novel therapeutic strategies including the protective use of oleuropein in gastric and lung cancers due to chemotherapy.

The carvacrol ameliorates acute pancreatitis-induced liver injury via antioxidant response.

Acute pancreatitis (AP) may cause significant persistent multi-organ dysfunction. Carvacrol (CAR) possesses a variety of biological and pharmacological properties. The aim of the present study was to analyze the hepatic protection of CAR on AP induced by cerulein and to explore the underlying mechanism using in vivo studies. The rats were randomized into groups to receive (1) no therapy; (2) 50 µg/kg cerulein at 1-h intervals by four intraperitoneal injection (i.p.); (3) 50, 100 and 200 mg/kg CAR by one i.p.; and (4) cerulein + CAR after 2 h of cerulein injection. 12 h later, serum was provided to assess the blood AST, ALT and LDH values. Also, liver tissues were obtained for histological and biochemical measurements. Liver oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as MDA and changes in tissue antioxidant enzyme levels, SOD, CAT and GSH-Px. Histopathological examination was performed using scoring systems. Oxidative damage to DNA was quantitated in studied tissues of experimental animals by measuring the increase in 8-hydroxydeoxyguanosine (8-OHdG) formations. We found that the increasing doses of CAR decreased pancreatitis-induced MDA and 8-OH-dG levels. Moreover, the liver SOD, CAT and GSH-Px activities in the AP + CAR group were higher than that of the rats in the AP group. In the treatment groups, AST, ALT and LDH were reduced. Besides, necrosis, coagulation and inflammation in the liver were alleviated (p < 0.05). We suggest that CAR could be a safe and potent new drug candidate for treating AP through its antioxidative mechanism of action for the treatment of a wide range of disorders related to hepatic dysfunction.

The biochemical and histological effects of lichens in normal and diabetic rats.

Oxidative stress plays an important role in causing diabetes; however, no studies have thoroughly reported on the toxic and beneficial effects of lichen extracts in patients with diabetes mellitus (DM). This study covers a previously unrecognized effect of two well-known lichen species Cetraria islandica and Pseudevernia furfuracae in streptozotocin (STZ)-induced diabetes. In experimental design, control or diabetic rats were either untreated or treated with aqueous lichen extracts (250-500 mg/kg /day) for 2 weeks starting at 72 h after STZ injection. On day 14, animals were anaesthetized, and metabolic and biochemical parameters were appreciated between control and treatment groups. The histopathology of liver was examined using three different staining methods: hematoxylin-eosin (H&E), periodic acid Schiff (PAS), and reticulin and Sudan Black B. Our experimental data showed that increasing doses of C. islandica and P. furfuracae alone did not have any detrimental effects on studied parameters and the malondialdehyde level of liver.C. islandicaextract showed positive results for antioxidant capacity compared to doses of P. furfuracae extract. However, the protective effect of C. islandica extract on diabetes-induced disorders and hepatic damages is still unclear. Moreover, unfortunately, animals subjected to DM therapy did not benefit from the usage of increasing lichen doses due to their unchanged antioxidant activity in tissues. The results obtained in present study suggested that C. islandica and P. furfuracae is safe but the power of these is limited because of intensive oxidative stress in liver of type 1 diabetic rats. It is also implied that C. islandica extract is especially suitable for different administration routes in DM animals.

Evaluating the toxic and beneficial effects of lichen extracts in normal and diabetic rats.

Lichens can be used as a novel bioresource for natural antioxidants. However, there is need for further investigations to validate the lichens used in medicinal remedies. In this study, the effects of Cetraria islandica and Pseudevernia furfuracae lichen species in streptozotocin (STZ)-induced diabetes were evaluated. Diabetic rats were treated with aqueous lichen extracts (250 and 500 mg/kg/day) for 2 weeks starting at 72 h after STZ injection. On the 14th day, animals were anesthetized, and then metabolic and biochemical parameters were evaluated between control and treatment groups. Pancreatic histology and ß-cell mass were examined by hematoxylin and eosin and insulin immunohistochemistry stainings. Our findings revealed that these lichen species could be used safely in this dose range. In addition, C. islandica extracts showed prominent results compared to the doses of P. furfuracae extract for antioxidant capacity. However, the protectivity of C. islandica extract was inadequate against diabetes-induced pancreatic damages via forming oxidative stress. In conclusion, the usage of C. islandica might serve for early intervening in the risk reduction of type 1 diabetes.

Carvacrol modulates oxidative stress and decreases cell injury in pancreas of rats with acute pancreatitis.

Acute pancreatitis (AP) is considered as major problem around the world and the incidence of AP is increasing. Carvacrol (CAR), a monoterpenic phenol, has good antioxidant activity. This in vivo study was designed to evaluate whether CAR provide protection against AP that developed by pancreas injury. The rats were randomised into groups to receive (I) no therapy; (II) 50 µg/kg cerulein at 1 h intervals by four intraperitonally (i.p.) injections; (III) 50, 100 and 200 mg/kg CAR by one i.p. injection; and (IV) cerulein plus CAR after 2 h of cerulein administration. 12 h later, serum samples were obtained to assess pancreatic function, the lipase and amylase values. The oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde (MDA) and changes in main tissue antioxidant enzyme levels including SOD, CAT and GSH-PX. Histopathological examination was performed using scoring systems. Additionally, oxidative DNA damage was determined by measuring the increases of 8-hydroxy-deoxyguanosine (8-OH-dG) formations. We found that the increasing doses of CAR decreased AP-induced MDA and 8-OH-dG levels. Moreover, the pancreas antioxidant enzyme activities were higher than that of the rats in the AP group when compared to the AP plus CAR group. In the treatment groups, the lipase and amylase were reduced. Besides, histopathological findings in the pancreatic tissue were alleviated (p < 0.05). We suggest that CAR could be a safe and potent new drug candidate for treating AP through its antioxidative mechanism of action for the treatment of a wide range of disorders related to pancreas.

The effects of lycopene on hepatic ischemia/reperfusion injury in rats.

There is a very little information about the protective effect of lycopene (LYC) against hepatic ischemia-reperfusion injury. The present study was designed to examine the possible protective effect of the strong antioxidant and anti-inflammatory agent, LYC, on hepatic ischemia/reperfusion injury. For this purpose, rats were subjected to 45 min of hepatic ischemia followed by 60 min of reperfusion period. LYC at the doses of 2.5 and 5 mg/kg body weight (bw) were injected intraperitoneally, 60 min prior to ischemia. Upon sacrification, hepatic tissue samples were used for the measurement of catalase (CAT) activity and malondialdehyde (MDA) levels. Also, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were assayed in serum samples. As a result of the use of LYC at the doses of 2.5 and 5 mg/kg bw; while improvements of the ALT, AST, LDH and MDA values were partial and dose-dependent, the improvement of CAT activity was total and dose-independent (p < 0.05). Our findings suggest that LYC has a protective effect against ischemia/reperfusion injury on the liver.

Preventive role of gallic acid on hepatic ischemia and reperfusion injury in rats.

There is little information about the hepatoprotective effects of gallic acid against ischemia-reperfusion (I/R) damage. Animals were subjected to I/R. Gallic acid at doses of 50 and 100 mg/kg body weight (bw) were injected as a single dose prior to ischemia. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels. At the same time alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed in serum samples and compared statistically. While the ALT, AST, LDH activities and MDA levels were significantly increased, CAT and GPx activities significantly decreased in only I/R-induced control rats compared to normal control rats (P < 0.05). Treatment with gallic acid at a dose of 100 mg/kg bw significantly decreased the ALT, AST, LDH activities and MDA levels, and markedly increased activities of CAT and GPx in tissue homogenates compared to I/R-induced rats with no treatment group (P < 0.05). In oxidative stress generated by hepatic ischemia-reperfusion, gallic acid contributes partially an alteration in the delicate balance between the scavenging capacity of antioxidant defense systems and free radicals in favour of the antioxidant defense systems in the body.

The effects of Cetraria islandica and Pseudevernia furfuracea extracts in normal and diabetic rats.

Lichens are symbiotic organisms composed of a fungus joined to a photosynthesizing partner that can be either an alga or a cyanobacterium. They can be used as a novel bioresource for natural antioxidants. However, there is also a need for further studies to validate the lichens used in medicinal remedies. This study covers a previously unrecognized effects of Cetraria islandica (CIAE) and Pseudevernia furfuracea (PFAE) in streptozotocin (STZ)-induced diabetes. In experimental design, control or diabetic rats were either untreated or treated with aqueous lichen extracts (250-500 mg/kg/day) for 2 weeks starting at 72 h after STZ injection. On day 14, animals were anesthetized, metabolic and biochemical parameters were appreciated between control and treatment groups. The histopathology of kidney was examined using four different staining methods: hematoxylin-eosin (H&E), periodic acid-Schiff (PAS), Masson trichrome and Congo red. Our experimental data showed that increasing doses of CIAE and PFAE did not have any detrimental effects on the studied parameters and the malondialdehyde level of kidney. CIAE extract showed prominent results compared to doses of PFAE extract for antioxidant capacity. However, the protective effect of CIAE extract was inadequate on diabetes-induced disorders and kidney damages. Moreover, animals subjected to diabetes mellitus (DM) therapy did not benefit unfortunately from the usage of increasing lichen doses due to their unchanged antioxidant activity to tissue. The results obtained in present study suggested that CIAE and PFAE are safe but the power of these is limited because of the intensive oxidative stress in kidney of type 1 diabetic rats. It is also implied that CIAE extract is especially suitable for different administration routes in DM.

Carvacrol partially reverses symptoms of diabetes in STZ-induced diabetic rats.

Little is known about the protective effects of carvacrol on the symptoms of streptozotocin induced diabetes in rats. Hence, this present study was designed to evaluate the protective effect of the strong antioxidant, carvacrol, on the symptoms of streptozotocin induced diabetes in rats. Carvacrol at the doses of 25 and 50 mg/kg body weight were orally administered to diabetic rats for a period of 7 days after the onset of diabetes. Food-water intake and body weight changes were daily recorded. Biochemical parameters such as serum glucose, insulin, total cholesterol, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were measured. Although treatment of diabetic rats with oral administration of carvacrol resulted in a slight reduction in serum glucose level and significant reduction in serum total cholesterol, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase in comparison with diabetic control rats, there were no significant differences in serum insulin levels, food-water intake values and body weight changes. Despite the inadequacy of carvacrol on diabetes treatments, it was determined to have at least a partially protective role on liver enzymes.

The hepatoprotective effects of Hypericum perforatum L. on hepatic ischemia/reperfusion injury in rats.

Little is known about the effective role of Hypericum perforatum on hepatic ischemia-reperfusion (I/R) injury in rats. Hence, albino rats were subjected to 45 min of hepatic ischemia followed by 60 min of reperfusion period. Hypericum perforatum extract (HPE) at the dose of 50 mg/kg body weight (HPE50) was intraperitonally injected as a single dose, 15 min prior to ischemia. Rats were sacrificed at the end of reperfusion period and then, biochemical investigations were made in serum and liver tissue. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels. At the same time alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed in serum samples and compared statistically. While the ALT, AST, LDH activities and MDA levels were significantly increased, CAT and GPx activities significantly decreased in only I/R-induced control rats compared to normal control rats (p < 0.05). Treatment with HPE50 significantly decreased the ALT, AST, LDH activities and MDA levels, and markedly increased activities of CAT and GPx in tissue homogenates compared to I/R-induced rats without treatment-control group (p < 0.05). In oxidative stress generated by hepatic ischemia-reperfusion, H. perforatum L. as an antioxidant agent contributes an alteration in the delicate balance between the scavenging capacity of antioxidant defence systems and free radicals in favour of the antioxidant defence systems in the body.

Effects of lichen extracts on haematological parameters of rats with experimental insulin-dependent diabetes mellitus.

The prevalence of diabetes mellitus in the world is steadily increasing. Oxidative stress contributes to the development of diabetic complications, including diabetic haematological changes. Lichens are used as food supplements and are also used as possible natural antioxidant, antimicrobial and anticancer agents. We hypothesized that antioxidant activity of lichens may decrease hyperglycaemia-induced oxidative stress and prevent the development of diabetic complications, including abnormality in haematological condition. Therefore, the effects of Cetraria islandica water extract (CIWE) and Pseudevernia furfuracea water extract (PFWE) on the haematological parameters of rats with type 1 DM were investigated for the first time in the present study. Control Sprague-Dawley or streptozotocin (STZ)-induced diabetic rats were either untreated or treated with water lichen extracts (5-500 mg/kg body weight (bw)/day) for 2 weeks, starting at 72 h after STZ injection. On day 14, animals were anaesthetized and haematological and metabolic parameters were determined between control and experimental groups. In addition, the total oxidative stress (TOS), a specific indicator of oxidative stress, and the total antioxidant capacity (TAC) were measured by biochemical studies. In diabetic rats, CIWE of 250-500 mg/kg bw dose showed more prominent results when compared with doses of PFWE for TAC. The results obtained in the present study suggested that the antioxidant activities of lichens might be the possible reason behind the observed antihaematological status. However, the protective effect of lichen extracts were inadequate on diabetes-induced microcytic hypochromic anaemia. In addition, the extracts have no effect on metabolic complications. Our experimental data showed that high doses of CIWE and PFWE alone have no detrimental effect on blood cells and TOS status of plasma. Hence, they are safe and suitable for different administration routes.

The ameliorative effect of Cetraria islandica against diabetes-induced genetic and oxidative damage in human blood.

CONTEXT: The aqueous extracts of Cetraria islandica (L.) Ach. (Parmeliaceae) is traditionally used in many countries against a number of conditions, including inflammatory conditions. OBJECTIVE: The present study aimed to assess, for the first time, the effectiveness of C. islandica in cultured primary blood cells of Type 1 diabetes subjects. MATERIALS AND METHODS: Diabetic and control blood samples were treated with or without aqueous lichen extract (5 and 10 µg mL(-1)) for 48 h. The activity of antioxidant enzymes in erythrocytes and also malondialdehyde levels in plasma were determined to evaluate the oxidative status. DNA damages were analyzed by SCE, MN and comet assays in cultured human lymphocytes. Additionally, proliferation index (PI) was evaluated in peripheral blood lymphocytes. RESULTS: There were significant increases in observed total DNA damage (comet assay) (240.2%) and SCE (168.8%), but not in MN frequencies of cultures with diabetes as compared (p > 0.05) to controls. Whereas, the significant reductions of total DNA damage (69.2 and 65.3%) and SCE frequencies (17.7 and 12.3%) were determined when the 5 and 10 mg mL(-1) lichen extract was added to the cell culture medium, respectively. However, lichen extract did not completely inhibit the induction of SCEs in lymphocytes of patients with diabetes. C. islandica extract was also useful on PI rates. DISCUSSION: In conclusion, the antioxidant role of C. islandica in alleviating diabetes-induced genomic instability and for increasing cell viability was firstly indicated in the present study.

The biochemical and histopathological investigation of amlodipine in ethylene glycol-induced urolithiasis rat model.

BACKGROUND: Urinary calculi are a common and severe problem, which are formed by urolithiasis or by the formation of calcium oxalate (CaOx) crystals in the kidneys. Many treatment options such as drugs, various herbal preparations, surgical removal of the stones, and extracorporeal shock wave lithotripsy have been applied for this condition. The aim of this study is to assess the effects of the drug amlodipine in an experimentally induced urolithiasis rat model. MATERIALS AND METHODS: The effect of 5 mg/kg amlodipine was studied in rats that were first treated with 1% ethylene glycol and 1% ammonium chloride for 21 days to induce urolithiasis. The weight differences and the levels of calcium, magnesium, and phosphate were measured in serum and urine. In addition, urine CaOx level was defined and histopathological analyses were performed on the kidneys. RESULTS: Urolithiasis caused a significant increase in both serum and urine parameters compared with healthy rats. Urolithiasis plus amlodipine administration increased the levels of these same parameters. Urine CaOx level was high in urolithiasis rats and was also increased by urolithiasis plus amlodipine administration. The weight of the rats decreased in the urolithiasis plus amlodipine group when compared with the urolithiasis group. Histopathological examinations revealed extensive intratubular crystal depositions and degenerative tubular structures in the urolithiasis group and the amlodipine treatment group. CONCLUSION: We showed that amlodipine may increase susceptibility to urolithiasis by raising hyperoxaluria and hypercalciuria. Further studies should be performed to elucidate the urolithiasis activity of amlodipine and to confirm the data.