Hispidulin exerts a protective effect against oleic acid induced-ARDS in the rat via inhibition of ACE activity and MAPK pathway.

This study investigates the protective role of Hispidulin on acute respiratory distress syndrome (ARDS) in rats. Rats were divided into three groups: control, ARDS, ARDS+ Hispidulin. The ARDS models were established by injecting rats with oleic acid. Hispidulin (100 mg/kg) was injected i.p. an hour before ARDS. Myeloperoxidase (MPO), Interleukin-8 (IL-8), Mitogen-activated protein kinases (MAPK), Lipid Peroxidation (LPO), Superoxide Dismutase (SOD), Glutathione (GSH), and Angiotensin-converting enzyme (ACE) were determined by ELISA. Tumor necrosis factor-alpha (TNF-α) expression was described by RT-qPCR. Caspase-3 immunostaining was performed to evaluate apoptosis. Compared with the model group, a significant decrease was observed in the MPO, IL-8, MAPK, ACE, LPO levels, and TNF-α expression in the ARDS+ Hispidulin group. Moreover, reduced caspase-3 immunoreactivity and activity of ACE were detected in the Hispidulin+ARDS group. The protective effect of Hispidulin treatment may act through inhibition of the ACE activity and then regulation of inflammatory cytokine level and alteration of apoptosis.

Hippophae rhamnoides Prevents Oleic Acid-Induced Acute Respiratory Distress Syndrome by Releasing Acetylcholinesterase Activity and Mitigation of Angiotensin-Converting Enzyme Level.

Hippophae rhamnoides exhibit a wide variety of medicinal and pharmacological effects. The present study aims to determine the role of ethanol extract of H. rhamnoides on oleic acid (OA)-induced acute respiratory distress syndrome (ARDS) in rats. Male rats were randomly divided into the following groups: (I) Control, (II) OA, and (III) OA+H. rhamnoides. H. rhamnoides extract (500 mg/kg) was given orally for 2 weeks before OA in Group III. Levels of total antioxidant capacity, total oxidant status (TOS), myeloperoxidase (MPO), mitogen-activated protein kinase (MAPK), acetylcholinesterase (AChE), and angiotensin-converting enzyme (ACE) were quantified by enzyme-linked immunosorbent assay (ELISA). Real time quantitative polymerase chain reaction was utilized to evaluate the expression of nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and matrix metalloproteinase 2 (MMP2). Also, Caspase-3 immunostaining and expression were performed to evaluate apoptosis. Compared with the OA group, there was a significantly decrease in the levels of MPO, TOS, MAPK, and ACE and in the expression of NF-κB, TNF-α, IL-6, MMP2, and Caspase-3 in the H. rhamnoides administration group. Moreover, the activity of AChE and level of TAS were substantially higher in the H. rhamnoides administration compared with the OA group. The findings in the study suggest that the protective effect of H. rhamnoides pretreatment may act through inhibition of the ACE activity, releasing AChE, regulation of inflammatory cytokine levels, and suppression of apoptotic process in ARDS.

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.

The hepato-renal protective potential of walnut seed skin extract against acute renal ischemia/reperfusion damage.

Acute kidney damage is defined as a sudden change in kidney functions that prevents the removal of nitrogenous wastes from the body, thus disrupting the body's fluid and electrolyte balance. When acute kidney injury occurs, the kidneys and liver are most affected in the body. Agents used in the treatment of acute kidney injury often have nonsteroidal anti-inflammatory properties that can produce toxic effects on the gastrointestinal tract and kidneys. Natural antioxidants can be recommended as an alternative to existing treatment or in combination to protect tissues against these toxic effects. Therefore, we conducted our current study on whether walnut seed skin (WSS) extract might have hepato-renal protective effects in kidney-damaged Sprague-Dawley rats. This study is the first to use walnut seed skin extract in liver and kidney tissues in renal ischemia/reperfusion (IR) injury. Female Sprague-Dawley rats were randomly divided into three groups: Healty control (HC), renal IR (50 min ischemia - 3 h reperfusion), and renal IR + 450 mg/kg/p.o. WSS extract (the rats were treated with WSS extract orally once 1 h before the IR procedure). For this purpose, blood, liver and kidney tissues of rats were used. In serum samples, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea and creatinine values were determined separately for the administration groups. We also performed histopathological studies on liver and kidney tissues. Finally, gene markers (endothelial nitric oxide synthase (eNOS), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), Caspase-4 and Caspase-9) determined to evaluate the anti-oxidant, anti-inflammatory and apoptotic effect of walnut seed skin were measured by q-RT PCR method. As a result of the study it was determined that pre-application of WSS extract improved the deteriorated serum parameters in rats with renal ischemia. In the histopathological analysis results, it was observed that WSS had a protective effect on kidney and liver tissue. In studies on gene expression, although there were different and contradictory results for liver and kidney tissue, we determined that WSS was more protective on liver tissue. In conclusion, the healing potential of WSS in renal and hepatic tissues seems to act by inhibiting the inflammatory response, oxidative stress and apoptosis. Therefore, the potential of this extract is remarkable and may serve as a potential therapeutic that may protect against acute organ damages due to renal IR.

A comparative study on aquatic toxicity of chemically-synthesized and green synthesis silver nanoparticles on daphnia magna.

The steady increase in the employment of silver nanoparticles (AgNPs) in consumer products entails the determination of the aquatic toxicity of AgNPs. Various AgNP characteristics including particle size, and shape, surface charge, and material have prominent effects on ecotoxicity. In the present study, we investigated the aquatic toxicity of chemically-synthesized AgNPs (Che-AgNPs) and green synthesis AgNPs (Gr-AgNPs) to Daphnia magna as a model organism. In each case, Che-AgNPs and Gr-AgNPs showed dose-dependent toxicity in the range of 5-50 ppb. It was also detected that the size and surface coverage material of AgNPs has a significant impact on the survival rate of D. magna. We also analyzed the expression of some genes related to detoxification and the reproductive system. These observations presented that in both NP types the significant alterations were detected in genes of the model organism in a dose-dependent manner.

The effect of lithium tetraborate as a novel cardioprotective agent after renal ischemia-reperfusion injury

Abstract Epidemiological studies suggest that acute kidney injury has certain effect on myocardial function. In this study, for the first time, we tested a boron compound namely lithium tetraborate an act as an anti-oxidant and anti-inflammatory agent in ischemia-reperfusion injury. For this, we employed an in vivo rat model with kidney ischemia reperfusion injury to evaluate cardiac injury to clarify the mechanisms of lithium tetraborate. The evaluation of cardiac injury through kidney artery occlusion and reperfusion rat model indicated that lithium tetraborate could (1) reduce oxidative stress-induced endothelial dysfunction; (2) attenuate the inflammatory response of cardiac cells; and (3) alleviate the apoptosis and necrosis of myocytes. In summary, lithium tetraborate demonstrates significant therapeutic properties that contribute to the amelioration of cardiac damage, and it could be a promising candidate for future applications in myocardial dysfunction.

Inula graveolens induces selective cytotoxicity in glioblastoma and chronic leukemia cells.

OBJECTIVE: Crude oil extracts, components of extracts, and ethanolic extracts of Inula graveolens possess various pharmacological activities on various cancer cells including antioxidative and antiproliferative effects. Aqueous extract of this species has not been investigated on the liquid malignancies and solid tumors with a high incidence of treatment refractoriness and poor survival outcomes such as glioblastoma and leukemia. Hence, the present study aimed to evaluate the cytotoxic efficiency of I. graveolens aqueous extracts on human glioblastoma multiforme and chronic myelogenous leukemia cell lines in comparison to non-cancerous primary rat cerebral cortex and human peripheral blood mononuclear cells. METHODS: The cells were treated with the extracts of I. graveolens (125-1000 µg/mL) for 48 h, the cellular viability was identified using 3'-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and lactate dehydrogenase release was measured to determine the cytotoxic potential. Total oxidant status and apurinic/apyrimidinic endodeoxyribonuclease 1 assays were used to determine the oxidative status of cells and DNA damage, respectively. RESULTS: I. graveolens showed selective cytotoxicity toward human glioblastoma multiforme and chronic myelogenous leukemia cell lines and exhibited a higher antiproliferative effect against cancer cells in comparison to non-cancerous cells. Moreover, it significantly reduced the apurinic/apyrimidinic endodeoxyribonuclease 1 levels on both cancer cell lines as compared with their control cells without changing the levels of an oxidative stress marker. CONCLUSION: The extracts of I. graveolens have anti-cancer potential on human glioblastoma multiforme and chronic myelogenous leukemia cell lines without causing oxidative stress.

The cytotoxic and apoptotic effects of beta-blockers with different selectivity on cancerous and healthy lung cell lines.

ß-blockers having specific affinities to ß-adrenergic receptors are routinely used to treat cardiovascular problems. Additionally, it has been demonstrated that these drugs can be effective in treating apoptosis-related diseases. The current study was conducted to investigate the cytotoxic and apoptotic effects of ß-1 selective esmolol, ß-2 selective ICI-118,551, and non-selective nadolol blockers on the cancerous and healthy lung cells. MTT test was used to evaluate cytotoxicity. Apoptotic actions were examined by using Annexin V-FITC/PI assay, JC-1 staining, ROS test, and the determination of the caspase-4 and -9, Bcl-2, Bax, Bax/Bcl-2, and JNK levels. Although the MRC-5 showed greater resistance than A549 cells, the ß-blockers at 150-250 µM exhibited different levels of cytotoxic effect on both lung cell lines. Esmolol was found to be the most ineffective blocker and the increases in Bcl-2 protein levels were appeared to be effective in resistance to this drug. The increases in reactive oxygen species (ROS) together with the increase in caspase-4 and Bax protein levels have been shown to play a role in ICI-118,551 induced lung cell death. Nadolol was the most effective blocker increasing the total apoptotic cell population in both lung cells, which was based on both mitochondrial and endoplasmic reticulum stress. When the selectivities of the ß-blockers are considered, it seems that ß-2 specific antagonism predominantly mediated the death of lung cells, and the overwhelming factors causing apoptosis mainly varied depending on the selectivity of the blockers.

Ameliorative effect of umbelliferone in remote organ injury induced by renal ischemia-reperfusion in rats.

We evaluated the ameliorative role of umbelliferone in kidney, heart, and lung damage induced by renal ischemia/reperfusion (I/R) injury in rats. Umbelliferone was given orally to rats 60 min before ischemia. Ischemia was induced for 50 min and then reperfusion for 3 hr. The antioxidant enzymes, myeloperoxidase (MPO) activity, malondialdehyde (MDA) content, and cytokine levels in the kidney, heart, and lung were measured by ELISA. Moreover, histopathological changes were monitored. Renal I/R-induced oxidative stress in the organs by decreasing antioxidant enzymes. However, umbelliferone pretreatment enhanced superoxide dismutase (SOD) and glutathione (GSH), levels, reduced MDA and MPO levels. Renal I/R increased in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) levels, and histopathological changes but these effects were inhibited with umbelliferone pretreatment. Furthermore, umbelliferone increased in nitric oxide synthase (eNOS) level under ischemia conditions. Our results indicated that pretreatment of umbelliferone-ameliorated damages in remote organ induced by renal I/R through suppressing oxidative stress and modulating inflammatory responses. PRACTICAL APPLICATIONS: kidney, heart, and lung damages induced by renal I/R in rats was alleviated by umbelliferone. The oral treatment of umbelliferone markedly reversed the oxidative stress, inflammation, and histopathological changes by increasing in the levels of SOD, GSH, and eNOS, decreasing in the levels of MDA, MPO, TNF-α, and IL-6 in distant organ injury induced by renal I/R. This study firstly revealed that umbelliferone has potent antioxidant and anti-inflammatory activity in the remote organ damages caused by renal I/R. Consequently, umbelliferone may be an alternative therapeutic agent for treating renal I/R-induced damages.

The targets of ß-sitosterol as a novel therapeutic against cardio-renal complications in acute renal ischemia/reperfusion damage.

This research is the first to use ß-sitosterol on myocardial and renal tissues in renal ischemia/reperfusion (IR) damage. Female Wistar rats were randomly divided into three groups: control (sham), renal IR (50 min ischemia - 3 h reperfusion), and renal IR + 150 mg/kg/p.o. ß-sitosterol (the rats were treated with ß-sitosterol orally once 1 h before the IR procedure). ß-Sitosterol pretreatment caused an increase in superoxide dismutase and glutathione activities and a decrease in malondialdehyde levels in the kidney and heart. Moreover, it alleviated histopathological changes and downregulated the levels of tumor necrosis factor-alpha and interleukin-6 and upregulated the levels of endothelial nitric oxide synthase. As conclusion, the potential of ß-sitosterol for renal and cardiac necrosis and apoptosis appears to act by limiting inflammatory response and oxidative stress. Thus, the potential of this compound is noteworthy and may serve as a potential therapeutic in the treatment of acute organ damages due to renal IR.

(1 → 3)-ß-d-glucan enhances the toxicity induced by Bortezomib in rat testis.

We aimed to determine the possible effects of the antioxidant agent (1 â†’ 3)-ß-D-glucan on bortezomib-induced rat testis damage. We used five groups of rats; control, (1 â†’ 3)-ß-D-glucan (75 mg/kg), bortezomib group, bortezomib + (1 â†’ 3)-ß-D-glucan groups (injection of (1 â†’ 3)-ß-D-glucan after bortezomib and sacrificed at 48th or 72nd h). The effects of these substances were assessed by measuring the levels of the antioxidant enzymes and LPO, and by performing immunohistochemical analysis with NF-κB. The histology of testis was evaluated using aniline blue staining. (1 â†’ 3)-ß-D-glucan leads to significant reductions in the levels of antioxidant enzymes and increased levels of LPO in testes. Moreover, it increased the NF-κB immunopositivity significantly in testis, especially in Bortezomib + (1 â†’ 3)-ß-D-glucan group at 48th h. The histological changes were observed in the bortezomib and/or (1 â†’ 3)-ß-D-glucan groups. Our results demonstrated that testis damage caused by the treatment with bortezomib was not eliminated by (1 â†’ 3)-ß-D-glucan and shockingly it increased the damage. PRACTICAL APPLICATIONS: The testis damage caused by the treatment with bortezomib was not eliminated by (1 â†’ 3)-ß-D-glucan and as a result, ß-1,3-(D)-glucan enhanced the toxicity by leading a decrease in the levels of GSH, SOD, and CAT, thus caused an elevation in the immunoreactivity of NF-κB and altered the histopathological changes by enhancing the toxic effects of bortezomib. The findings of the previous studies about the antioxidative activity of (1 â†’ 3)-ß-D-glucan are controversial. So, it is necessary to consider the cytotoxicity of (1 â†’ 3)-ß-D-glucan in testis tissue. Thus, more studies on testis tissue are necessary to confirm that (1 â†’ 3)-ß-D-glucan is safe as an antioxidant.

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.

The efficacy of oleuropein against non-steroidal anti-inflammatory drug induced toxicity in rat kidney.

Indomethacin is generally used in clinical therapeutics as a non-steroidal anti-inflammatory drug. However, its use has been limited due to the gastrointestinal and renal toxic effects of this drug. These toxic effects were associated with not only the inhibition of prostaglandin synthesis but also drug-elevated oxidative stress. To ameliorate these toxicities, natural antioxidants can be used as an alternative and/or combination therapies. Therefore, the current study was conducted to assess the renoprotective effects of oleuropein against indomethacin-induced renal damages. Male Sprague-Dawley rats were pretreated with oleuropein (75, 150, and 300 mg/kg), and then treated with indomethacin (25 mg/kg). To evaluate kidney function, serum blood urea nitrogen, uric acid, and creatinine were measured. In addition, prostaglandin E2 , tumor necrosis factor-alpha, endothelial nitric oxide synthase, caspase-3, oxidant/antioxidant status, and 8-Oxo-2'-deoxyguanosine levels were determined for the antioxidative and anti-inflammatory effects of oleuropein. Tissue sections were also histopathologically assessed. The biochemical and histopathological analysis proved the toxic effects of indomethacin on kidney. However, the pretreatment with oleuropein (300 mg/kg) protects kidney from indomethacin-induced damages. Our study proved that prior administration of oleuropein has renoprotective activity against indomethacin-associated toxicities.

Antioxidant and anticancer activities of extract of Inula helenium (L.) in human U-87 MG glioblastoma cell line.

AIMS: The aim of this study is to explore the antioxidant and antiproliferative activities of aqueous extract from aerial parts of Inula helenium (L.) against human U-87 MG glioma cell line. MATERIALS AND METHODS: The 3'-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays were used to study antiproliferative and cytotoxic activities against U-87 MG cell after 48 h exposure. In addition, to assess the oxidative effects, total antioxidant capacity and total oxidant status levels were also measured. RESULTS: Finally, the aqueous extracts displayed antiproliferative and cytotoxic activities at high concentrations tested, particularly at 200 µg/ml, without causing to oxidative stress. CONCLUSION: The results strengthen the evidence that I. helenium could be considered a natural resource of potential antitumor agents for brain cancer. In addition, this study is expected to expand the existing information on the anticancer activity of I. helenium and to assist in a more focused design of further research as chemotherapeutic agents.

Therapeutic effects of oleuropein on cisplatin-induced pancreas injury in rats.

AIMS: Cisplatin (CIS) is an influential chemotherapeutic agent in the treatment of several types of malignant solid tumors, but its clinical use is related with ototoxicity. Oleuropein (OLE) is a natural antioxidant and scavenging free radicals. Here, we first explore the efficacy of OLE in pancreas against to the toxicity of CIS and also analyses its mechanism. MATERIALS AND METHODS: Fifty-six Sprague-Dawley rats were equally divided into eight groups, including, control group which received 7 mg/kg/day CIS intraperitoneally (i.p.) for 24 h, groups treated with doses of 50, 100, and 200 mg/kg OLE i.p. for 3 days, and groups which received same dose of CIS with three doses of OLE. After the treatments, animals were sacrificed. The oxidative DNA damage (8-hydroxy-2'-deoxyguanosine [8-OHdG]), total oxidative stress (TOS), total antioxidant status (TAS), and malondialdehyde (MDA) levels were evaluated in the pancreas. The histopathology of the pancreas was examined using three different staining methods: hematoxylin-eosin, periodic acid-Schiff, and alcian blue. Serum was provided to assess pancreatic function the lipase and amylase values. RESULTS: The results showed that CIS significantly increased the level of TOS, MDA, and 8-OHdG in tissue as compared to the control group. Moreover, severe tissue damages were detected in the pancreas. Whereas, OLE at high dose significantly decreased the formations of 8-OHdG, the level of MDA, and increased levels of TAS in tissue samples. In the CIS group, the levels of amylase and lipase increased compared with the control group. However, there were statistically significant differences among the CIS group and the CIS + OLE groups in the values of both amylase and lipase. In addition, histopathological findings observed in CIS group in the pancreatic tissue alleviated in CIS + OLE groups. CONCLUSION: We hope that the results of this study will provide an impetus for future investigations of novel treatment strategies for OLE in pancreas due to CIS.

Hepatoprotective Role of Thymol in Drug-Induced Gastric Ulcer Model.

INTRODUCTION AND AIM: Indo is widely one of the non-steroidal anti-inflammatory drugs and one of the common toxic effects of this drug is hepatic failure. Thymol is a monoterpene phenol with many different pharmacological activities. However, up to now its hepatoprotective effects on Indo-induced gastric ulcer model in rats have not been explored yet. MATERIAL AND METHODS: Thirty five Sprague-Dawley rats were divided into seven groups: control, ulcer control (30 mg/kg Indo), Indo + reference standard (50 mg/kg Rantidine), Indo + Thymol (75, 100, 250 and 500 mg/kg) groups. 10 minutes after the induction of ulcer with Indo; Thymol was orally administered to the rats. Liver function enzymes (AST, ALT and LDH) were measured from serum samples. TOS/TAC, TNF-α and PGE2 levels, eNOS and Caspase-3 activity were assessed from tissue homogenate samples. In addition, histopathologic analysis on liver sections was performed. RESULTS: Indo significantly increased the levels of hepatic enzymes, TNF-α and eNOS, and caspase-3 activation, while decreased PGE2 levels. Furthermore, it induced oxidative stress as evidenced by elevated TOS and decreased TAC levels. However, Thymol treatment induced a significant improvement in these parameters, especially in 250 mg/kg dose. On the other hand, treatment with Thymol 500 mg/kg dramatically affected the parameters much worse than the Indo treated group. CONCLUSION: The findings of the current study demonstrated that Thymol administration significantly ameliorated liver injury due to Indo toxicity. This effect of Thymol (250 mg/kg) may be mediated by its anti-oxidative or anti-inflammatory effect, and up-regulation the synthesis of PGE2.

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.