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.

Gossypin mitigates oxidative damage by downregulating the molecular signaling pathway in oleic acid-induced acute lung injury.

One of the leading causes of acute lung injury, which is linked to a high death rate, is pulmonary fat embolism. Increases in proinflammatory cytokines and the production of free radicals are related to the pathophysiology of acute lung injury. Antioxidants that scavenge free radicals play a protective role against acute lung injury. Gossypin has been proven to have antioxidant, antimicrobial, and anti-inflammatory properties. In this study, we compared the role of Gossypin with the therapeutically used drug Dexamethasone in the acute lung injury model caused by oleic acid in rats. Thirty rats were divided into five groups; Sham, Oleic acid model, Oleic acid+Dexamethasone (0.1 mg/kg), Oleic acid+Gossypin (10 and 20 mg/kg). Two hours after pretreatment with Dexamethasone or Gossypin, the acute lung injury model was created by injecting 1 g/kg oleic acid into the femoral vein. Three hours following the oleic acid injection, rats were decapitated. Lung tissues were extracted for histological, immunohistochemical, biochemical, PCR, and SEM imaging assessment. The oleic acid injection caused an increase in lipid peroxidation and catalase activity, pathological changes in lung tissue, decreased superoxide dismutase activity, and glutathione level, and increased TNF-α, IL-1ß, IL-6, and IL-8 expression. However, these changes were attenuated after treatment with Gossypin and Dexamethasone. By reducing the expression of proinflammatory cytokines and attenuating oxidative stress, Gossypin pretreatment provides a new target that is equally effective as dexamethasone in the treatment of oleic acid-induced acute lung injury.

Protective effects of a natural product, paeoniflorin, on ischemia reperfusion injury on rat ovary tissue: histopathological, immunohistochemical, and biochemical study.

In this study, the main hypothesis is that paeoniflorin may inhibit some cellular processes such as oxidative stress and inflammation. For this reason, we aimed to investigate the potential protective effects of a natural compound, paeoniflorin, on rat model of ovarian ischemia-reperfusion injury by detecting the oxidative stress parameters and inflammatory process parameters. 42 female Wistar-albino rats were divided into 6 random groups. The rats were subjected to 3-hour ischemia and 3-hour reperfusion process. Then, paeoniflorin at doses of 25, 50 and 100 mg/kg were applied 30 min before the reperfusion. The levels of pro-inflammatory (IL-1-ß, IL-6, TNF-α) and anti-inflammatory (IL-10, TGF-ß) cytokines were measured by ELISA. Similarly, IL-6, IL-10, TNF-α, NF-κB p65) positivity rates were detected by immunohistochemical staining. Additionally, oxidative stress parameters (MDA, GSH, SOD) were measured by tissue biochemistry. Ischemia-reperfusion injury caused significant increase in the levels of SOD, MDA, TNF-α, IL-1-ß, IL-6 and NF-κB p65, while paeoniflorin treatments improved the related parameters in a dose-dependent manner. As a conclusion, our findings support the evidence that paeoniflorin has a potential protective effects on ovarian ischemia-reperfusion injury. Further detailed studies should be performed to shed light the molecular mechanism of these protective effects.

Dietary effect of grape (Vitis vinifera) seed extract mitigates hepatic disorders caused by oxidized fish oil in rainbow trout (Oncorhynchus mykiss).

The major goal of this study was to determine the effect of grape seed extract (GSE) on liver damage in rainbow trout (Oncorhynchus mykiss) that was caused by the consumption of dietary oxidized fish oil (OFO). Rainbow trout were fed six different experimental diets coded OX-GSE 0 (OFO diet), OX-GSE 1 (OFO and 0.1% GSE), OX-GSE 3 (OFO and 0.3% GSE), GSE 0 (fresh fish oil and 0.0% GSE), GSE 1 (fresh fish oil and 0.1% GSE), and GSE 3 (fresh fish oil and 0.3% GSE) for 30 days. The lowest % hepatosomatic index (HSI) result was calculated in fish fed with OX-GSE 0 and the highest HSI was determined in fish fed with GSE 1 diets (p < 0.05). Histopathologically, hydropic degeneration in hepatocytes significantly increased OX-GSE 0 and GSE 3 compared to GSE 1 diets (p < 0.05). Deposition of lipid droplets in hepatocytes was significantly increased in OX-GSE 0 and OX-GSE 3 groups than others (p < 0.05). Liver biochemistry parameters such as superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) were significantly affected by OX and GSE treatments (p < 0.05). There were significant differences in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) among the liver enzymes analyzed in serum in OX and GSE (p < 0.05), meanwhile no difference was observed in lactate dehydrogenase (LDH) values between groups (p > 0.05). In conclusion, liver biochemistry and histopathology of rainbow trout consuming diets containing oxidized fish oil were negatively affected. However, it was determined that the supplementation of 0.1% GSE to the diet had a significant ameliorative role in these adverse effects.

Two flavonoids, baicalein and naringin, are effective as anti-inflammatory and anti-oxidant agents in a rat model of polymicrobial sepsis.

INTRODUCTION: In this study, our aim was to investigate the possible protective and therapeutic effects of these two flavonoids, baicalein, and naringin, in 50 and 100 mg/kg doses applied both before and after cecal ligation and puncture (CLP) procedures in a polymicrobial sepsis rat model, and evaluate the possible contribution of oxidative and inflammatory markers by immunological, biochemical, molecular, and histopathological methods. METHODS: Sixty-six Wistar albino rats were divided into 11 groups. The pro-inflammatory (TNF-alpha, IL-1-beta, and IL-6) and anti-inflammatory (TGF-beta and IL-10) cytokine levels were measured by ELISA technique. CD3, CD68, and nuclear factor kappa B positivity rates were detected by immunohistochemical methods. Oxidative stress parameters (MDA, SOD, and GSH) were measured by tissue biochemistry. RESULTS: Sepsis caused a significant increase in all pro-inflammatory cytokine levels and MDA activity. Also, it led to an increase in the positivities of CD3, CD68, and NF-κB markers. However, especially pre-CLP doses of baicalein and naringin inhibited the inflammation process by suppressing pro-inflammatory and increasing anti-inflammatory cytokine levels, as well as regulating the oxidative stress process by normalizing the oxidant/anti-oxidant enzyme levels. CONCLUSION: Both pre- and post-application of baicalein and naringin are quite effective to prevent sepsis-caused cellular processes. This protective and therapeutic effects by baicalein and naringin in animals with sepsis seems to be originated from the high antioxidant capacity and inhibition of pro-inflammatory cytokine production. Thus, those natural agents may prove to be valuable protective agent against septic shock.

Effects of tocilizumab and dexamethasone on the downregulation of proinflammatory cytokines and upregulation of antioxidants in the lungs in oleic acid-induced ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening disease caused by the induction of inflammatory cytokines and chemokines in the lungs. There is a dearth of drug applications that can be used to prevent cytokine storms in ARDS treatment. This study was designed to investigate the effects of tocilizumab and dexamethasone on oxidative stress, antioxidant parameters, and cytokine storms in acute lung injury caused by oleic acid in rats. METHODS: Adult male rats were divided into five groups: the CN (healthy rats, n = 6), OA (oleic acid administration, n = 6), OA + TCZ-2 (oleic acid and tocilizumab at 2 mg/kg, n = 6), OA + TCZ-4 (oleic acid and tocilizumab at 4 mg/kg, n = 6), and OA + DEX-10 (oleic acid and dexamethasone at 10 mg/kg, n = 6) groups. All animals were euthanized after treatment for histopathological, immunohistochemical, biochemical, PCR, and SEM analyses. RESULTS: Expressions of TNF-α, IL-1ß, IL-6, and IL-8 cytokines in rats with acute lung injury induced by oleic acid were downregulated in the TCZ and DEX groups compared to the OA group (P < 0.05). The MDA level in lung tissues was statistically lower in the OA + TCZ-4 group compared to the OA group. It was further determined that SOD, GSH, and CAT levels were decreased in the OA group and increased in the TCZ and DEX groups (P < 0.05). Histopathological findings such as thickening of the alveoli, hyperemia, and peribronchial cell infiltration were found to be similar when lung tissues of the TCZ and DEX groups were compared to the control group. With SEM imaging of the lung tissues, it was found that the alveolar lining layer had become indistinct in the OA, OA + TCZ-2, and OA + TCZ-4 groups. CONCLUSIONS: In this model of acute lung injury caused by oleic acid, tocilizumab and dexamethasone were effective in preventing cytokine storms by downregulating the expression of proinflammatory cytokines including TNF-α, IL-1ß, IL-6, and IL-8. Against the downregulation of antioxidant parameters such as SOD and GSH in the lung tissues caused by oleic acid, tocilizumab and dexamethasone upregulated them and showed protective effects against cell damage.

(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.

Evaluation of the Roflumilast Effect Supplemented with Linezolid in Pleural Empyema in Rats Caused by Intrapleural Staphylococcus aureus Inoculation.

In addition to tube drains, pleural empyema is treated with antibiotics and anti-inflammatory drugs. We aimed to evaluate the anti-inflammatory activity of roflumilast combined with linezolid in a rat model of pleural empyema induced by Staphylococcus aureus. A total of 40 rats were divided into 7 groups: sham (n = 4), S. aureus inoculation (n = 6), S. aureus + 10 mg/kg linezolid (n = 6), S. aureus + 5 mg/kg roflumilast (n = 6), S. aureus + 10 mg/kg linezolid + 5 mg/kg roflumilast (n = 6), S. aureus + 10 mg/kg roflumilast (n = 6), and S. aureus + 10 mg/kg linezolid + 10 mg/kg roflumilast (n = 6). Animals were administered linezolid 1 h before and 12 h after inoculation with S. aureus. Roflumilast was administered orally as a single dose 30 min before inoculation with S. aureus. Compared to linezolid treatment alone, linezolid combined with 5 mg/kg roflumilast significantly improved TNF-α, IL-1ß, vasodilation/congestion, and tissue/pleural polynuclear leukocyte (PNL) infiltration (p < 0.05). Linezolid combined with 10 mg/kg roflumilast also provided a significant improvement in TNF-α, IL-1ß, IL-6, endothelin-1, vasodilation/congestion, mesothelial cell damage, lung tissue PNL, and pleural PNL compared to linezolid alone (p < 0.05). Due to its anti-inflammatory effects and significant impact on recovery, roflumilast can be used in conjunction with antibiotherapy for the treatment of pleural empyema.

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.

The Protection Potential of Antioxidant Vitamins Against Acute Respiratory Distress Syndrome: a Rat Trial.

Acute respiratory distress syndrome (ARDS) is a fatal disease that includes inflammation formed by septic and non-septic causes. Reactive oxygen radicals (ROS) play a key role in ARDS pathophysiology and constitute the base of damage process. Antioxidant vitamins are used for inhibiting hazardous effects of radicals. Therefore, effects of antioxidant vitamins such as α-lipoic acid (ALA), vitamin E (VITE), and C (VITC) were investigated on oleic acid (OA)-induced ARDS rat model. Furthermore, high and low dose of methylprednisolone (HDMP, LDMP) was used for comparing effects of the vitamins. In this study, 42 male rats were divided to seven groups named control, OA, ALA, VITE, VITC, LDMP, and HDMP. OA was intravenously administered to all groups except control group and other compounds were orally administered (ALA, VITE, and VITC: 100 mg/kg, LDMP: 5 mg/kg, HDMP: 50 mg/kg) after OA injections. OA increased MDA level in lung tissue and TNF-α and IL-1ß cytokine levels in serum. ALA, VITE, VITC, and both dose of MP significantly decreased the cytokine levels. Although OA reduced SOD, CAT, and GSH levels in lung tissue, the vitamins and LDMP markedly enhanced the levels except for HDMP. Furthermore, OA showed thickening in bronchi and alveolar septum, hyperemia in vessels, and inflammatory cell infiltrations in lung tissue histopathological examinations. Antioxidant vitamins may be useful for premedication of ARDS and similar disorders. However, methylprednisolone was not found sufficient for being a therapeutic agent for ARDS.

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.

Anti-inflammatory and antioxidant properties of jervine, a sterodial alkaloid from rhizomes of Veratrum album.

BACKGROUND: Veratrum, hellebore is an important plant species of the Liliaceae family and jervine is the characteristic steroidal alkaloid constituent of Veratrum album. PURPOSE: In the current study, anti-inflammatory and antioxidant effects of jervine isolated from NH4OH-benzene extract of V. album rhizomes were investigated on CAR induced paw edema in rats. METHODS/STUDY DESIGN: In inflammatory study, 50, 100, 200 and 400  mg/kg doses of jervine, 25  mg/kg doses of DIC and IND were orally administered, and the volume of the foots were measured up to their knee arthrosis by plethismometer. After one hour of the oral administration of the all treatments, 0.1 ml of CAR solution (1%) was injected into the foot of the all rat groups and the volume of the foots were measured during 5 h after CAR injection. GPx, SOD, GR, MPO, CAT enzymes activities and GSH, LPO levels of the supernatants of paw homogenates and inflammation biomarkers such as TNF-α and IL-1ß in the rats serums were also estimated. RESULTS: According to the present results, jervine exerted 50.4-73.5% anti-inflammatory effects in carrageenan induced paw edema. Inflammation biomarkers such as TNF-α, IL-1ß and MPO that increased by CAR injection were suppressed by the administrations of all doses of jervine, IND and DIC. In all paw tissues, LPO levels as indicator of oxidative tissue damage were found to be high in CAR-treated group and it was found to be decreased in all doses of jervine. CONCLUSION: Jervine, DIC and IND reduced the negative effects of CAR due to increasing effects on the SOD, CAT, GSH, GPx and GR antioxidants.

Effect of melatonin on antioxidant capacity, inflammation and apoptotic cell death in lung tissue of diabetic rats.

PURPOSE: To investigate the effects of melatonin on antioxidant capacity, inflammation and apoptotic cell death (through expression of cleaved-caspase 3) in lung tissue samples of diabetic rats. METHODS: Thirty male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control group) was made up of healthy rats. Group 2 (diabetes group) received streptozotocin at a dose of 50 mg/kg/day for 5 days.Group 3 (diabetes plus melatonin group) received streptozotocin at a dose of 50 mg/kg/day for 5 days and then they received melatonin at a dose of 20 mg/kg/day between 28thand 35thdays of the study. RESULTS: Tissue MDA and MPO levels were found to be significantly higher in diabetes group compared to control group (p<0.05) whilst administration of melatonin was found to significantly lower this increase down to normal levels (p<0.05). Bronchus associated lymphoid tissue (BALT) was more severe in diabetics whereas administration of melatonin alleviated this hyperplasia. Cleaved caspase 3 activity was severe in hyperplastic BALT in diabetic rats however in lowered down to moderate level when melatonin was administered. CONCLUSION: The melatonin caused an increase in antioxidant capacity and decreased the expression of cleaved-caspase 3.

Effect of melatonin on antioxidant capacity, inflammation and apoptotic cell death in lung tissue of diabetic rats

Abstract Purpose: To investigate the effects of melatonin on antioxidant capacity, inflammation and apoptotic cell death (through expression of cleaved-caspase 3) in lung tissue samples of diabetic rats. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control group) was made up of healthy rats. Group 2 (diabetes group) received streptozotocin at a dose of 50 mg/kg/day for 5 days.Group 3 (diabetes plus melatonin group) received streptozotocin at a dose of 50 mg/kg/day for 5 days and then they received melatonin at a dose of 20 mg/kg/day between 28thand 35thdays of the study. Results: Tissue MDA and MPO levels were found to be significantly higher in diabetes group compared to control group (p<0.05) whilst administration of melatonin was found to significantly lower this increase down to normal levels (p<0.05). Bronchus associated lymphoid tissue (BALT) was more severe in diabetics whereas administration of melatonin alleviated this hyperplasia. Cleaved caspase 3 activity was severe in hyperplastic BALT in diabetic rats however in lowered down to moderate level when melatonin was administered. Conclusion: The melatonin caused an increase in antioxidant capacity and decreased the expression of cleaved-caspase 3.

A novel therapeutics agent: antioxidant effects of hydroxylfasudil on rat kidney and liver tissues in a protamine sulphate-induced cystitis rat model; preliminary results.

Cystitis is defined as an inflammation of the bladder caused by a bacterial infection, and it can be dangerous and painful when it spreads through the internal organs. In this study, antioxidant effects of hydroxylfasudil (HF) at the enzymatic and molecular level on kidney and liver tissues in cystitis rat model, which is caused by inflammation of the rat bladder with a protamine sulphate (PS), was examined. Quantitative changes of reduced glutathione (GSH) and lipid peroxidation (LPO) levels, which are a marker for oxidative stress, were determined in rat kidney and liver tissues for each groups. And then molecular and biochemical impact of HF treatment on antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT) in cystitis model were studied. The results suggest that HF could be beneficial to the renal and hepatic antioxidant system. Thus, HF might be used as a novel therapeutics agent to eliminate interstitial cystitis.

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.

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.

Natural product inhibitors of carbonic anhydrase I and II isoenzymes: osajin and pomiferin.

The aim of this study is to purify carbonic anhydrase I and II isoenzymes from human erythrocyte, isolate two natural products osajin (OSJ) and pomiferin (PMF) from Maclura pomifera fruits, and evaluate the in vitro effect of these natural metabolites on these isoenzymes. These natural products may be used as starting points for drug discovery (like drugs used in several therapeutic applications, including antiglaucoma activity). For the purification procedure, the Sepharose-4B-l-tyrosine-sulphonamide affinity chromatography was used. Column chromatography and thin layer chromatography methods were used for isolation of OSJ and PMF from M. pomifera fruits and their chemical structures were elucidated by IR, 1D, and 2D NMR methods. We compared inhibitory effects of these natural products with inhibitory effects of phenolic compounds and found that these products demonstrated average inhibition effects. We thought that this study will give inspiration to scientists interested in this issue.