Hepatoprotective role of myricitrin isolated from Mimusops elengi Linn. leaves extract on γ-radiation-induced liver damage in rats: Phyto-biochemical investigations.

The hepatoprotective effects of methanol extract of Mimusops elengi Linn. (M. elengi L.) leaves and isolated pure myricitrin (3-, 4-, 5-, 5, 7-five hydroxyflavone-3-O-α-l-rhamnoside) (Myr) were evaluated in male rats exposed to γ-irradiation. The extraction of M. elengi L. leaves was performed using ethyl acetate (EtOAC). Seven groups of rats were used: control group, irradiated (IRR) group (6 Gy of γ-rays in a single dose), vehicle group (oral administration of 0.5% carboxymethyl cellulose for 10 days), EtOAC extract group (100 mg/kg body weight of extract, orally for 10 days), EtOAC + IRR group (administration of extract and exposure to γ-rays on Day 7), Myr group (50 mg/kg body weight Myr, orally for 10 days), and Myr + IRR group (administration of Myr and exposure to γ-rays on Day 7). High-performance liquid chromatography and 1H-nuclear magnetic resonance were used to isolate and characterize the compounds from M. elengi L. leaves. Enzyme-linked immunosorbent assay was used for biochemical analyses. Identified compounds were Myr, myricetin 3-O-galactoside, myricetin 3-O-rahmnopyranoside (1 → 6) glucopyranoside, quercetin, quercitol, gallic acid, α-,ß-amyrin, ursolic acid, and lupeol. Serum aspartate transaminase and alanine transaminase activities were significantly increased, while serum protein and albumin levels were significantly decreased after irradiation. Hepatic levels of tumor necrosis factor-α, prostaglandin 2, inducible nitric oxide synthase, interleukin-6 (IL-6), and IL-12 were increased following irradiation. Improvements were observed in most serological parameters after treatment with extract or pure Myr, with histological analyses confirming decreased liver injury in treated rats. Our study demonstrates that pure Myr has a greater hepatoprotective effect than M. elengi leaf extracts against irradiation-induced hepatic inflammation.

UPLC-ESI-MS/MS profiling and hepatoprotective activities of Stevia leaves extract, butanol fraction and stevioside against radiation-induced toxicity in rats.

Stevioside is the major component of Stevia rebaudiana (Bertoni) leaves, family Asteraceae. UPLC-ESI-MS/MS analyses of leaves total methanol extract (TEx) and standardized butanol fraction (BF, 113.5 mg stevioside/g) were performed herein, revealing steviol glycosides, caffeoylquinic acid derivatives, flavonoids, and sesquiterpenoids. Their hepatoprotective activities against radiation-induced toxicity were evaluated compared to pure stevioside. Rats pretreatment with stevioside, TEx, and BF orally for 7 days before subjection to 6.5 Gy whole-body-gamma-irradiation reversed histopathological damages; improved liver functions and restored depleted antioxidants. ALT and reduced-glutathione levels showed insignificant changes, compared to control, by (5.22%, 3.20%, 24.90%) and (-0.47%, -3.95%, -2.63%), respectively. Glutathione-S-transferase, catalase, and MDA levels were significantly ameliorated. Liver tissue molecular profiling showed reduction in elevated TNF-α by 23.83%, 29.06%, 28.34%, respectively, and in NF-kB and COX-2 expression levels via immunohistochemical study. BF showed better hepatoprotective activity than TEx which may be attributed to higher stevioside, flavonoids, and caffeoylquinic acid derivatives content.

Radiosensitizing Effect of Bromelain Using Tumor Mice Model via Ki-67 and PARP-1 Inhibition.

Recent reports have shown that bromelain (BL), a pineapple extract, acts as an adjuvant therapy in cancer treatment and prevention of carcinogenesis. The present study was designed to investigate the possible mechanisms by which BL could radiosensitize tumor cells in vitro and in a mouse tumor model. BL has shown a significant reduction in the viability of the radioresistant human breast carcinoma (MCF-7) cell line using cell proliferation assay. The in vivo study was designed using the Ehrlich model in female albino mice, treated with BL (6 mg/kg b. wt., intraperitoneal, once daily for 10 days) 1 hour before exposure to a fractionated dose of gamma radiation (5 Gy, 1 Gy for 5 subsequent days). The radiosensitizing effect of BL was evident in terms of a significant reduction in tumor volume, poly ADP ribose polymerase-1 (PARP-1), the proliferation marker Ki-67 and nuclear factor kappa activated B cells (NF-κB) with a significant elevation in the reactive oxygen species (ROS) content and lipid peroxidation (LPO) in tumor cells. The present findings offer a novel insight into the radiosensitizing effect of BL and its potential application in the radiotherapy course.

Low dose gamma irradiation attenuates cyclophosphamide-induced cardiotoxicity in rats: role of NF-κB signaling pathway.

PURPOSE: Cyclophosphamide (Cyp) is one of the most commonly used, wide spectrum chemotherapeutic agents. Cyp has multi-organ toxicities that are dose limiting, thus it's mostly used in chemotherapeutic combinations. Radiation is well known as a hazardous sort of energy, recent studies are interested in studying the beneficial therapeutic effects of low-dose gamma radiation. This study examined the protective effect of two different doses/dose-rates of irradiation either alone or combined with telmisartan against Cyp-induced cardiotoxicity. MATERIALS AND METHODS: Rats were divided into seven groups; (1): Control, (2): Cyp, (3-4): 0.05 Gy low dose rate (LDR) irradiation, 0.25 Gy high dose rate (HDR) irradiation, respectively, prior to Cyp dose, (5-7): telmisartan either alone or with 0.05 Gy LDR-irradiation or 0.25 Gy HDR-irradiation, respectively, prior to Cyp dose. The current investigation studied the effect of Cyp alone or combined with different treatment regimens on serum cTn-I and LDH, nuclear factor-κB (NF-κB) pathway (p65/IκB/IKK-α/IKK-ß) in the myocardium. Pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α were assessed in addition to histopathological examination of the heart. RESULTS: Low-dose irradiation attenuated cardiac enzymes, pro-inflammatory cytokines, NF-κB content, and histology, in both low and HDRs. Furthermore, the combination of low-dose irradiation with telmisartan (an angiotensin-II receptor type-1 blocker and a known cardio-protective drug) offered the best histological results. CONCLUSIONS: Low-dose irradiation-induced amelioration is partially but not completely through canonical activation of NF-κB, and may have another atypical pathway. While telmisartan probably ameliorates NF-κB totally through canonical pathway.

Study of the Radiosensitizing and Radioprotective Efficacy of Bromelain (a Pineapple Extract): In Vitro and In Vivo.

This study hypothesizes that, bromelain (BL) acts as radiosensitizer of tumor cells and that it protects normal cells from radiation effects. In vitro and in vivo studies have been carried out to prove that assumption. In vitro MTT cell proliferation assay has shown that the irradiated Ehrlich ascites carcinoma (EAC) cell line could be sensitized by BL pretreatment. In vivo: animals were randomly divided into 5 groups, Group 1: control (PBS i.p for 10 days), Group 2: Ehrlich solid tumor (EST) bearing mice, Group 3: EST + γ-radiation (fractionated dose, 1 Gy × 5), Group 4: EST + BL (6 mg/kg, i.p), daily for 10 days, Group 5: EST + BL for 10 days followed by γ-irradiation (1 Gy × 5). The size and weight of tumors in gamma-irradiated EST bearing mice treated with BL decreased significantly with a significant amelioration in the histopathological examination. Besides, BL mitigated the effect of γ-irradiation on the liver relative gene expression of poly ADP ribose polymerase-1 (PARP1), nuclear factor kappa activated B cells (NF-κB), and peroxisome proliferator-activated receptor α (PPAR-α), and it restored liver function via amelioration of paraoxonase1 (PON1) activity, reactive oxygen species (ROS) content, lipid peroxidation (LPO) and serum aspartate transaminase (AST), alanine transaminase (ALT), and albumin (ALB). It is concluded that BL can be considered as a radio-sensitizer and radio-protector, suggesting a possible role in reducing radiation exposure dose during radiotherapy.

Therapeutic implications of assessment of serum zinc levels in patients with vitiligo: A patient controlled prospective study.

Vitiligo is an autoimmune disease characterized by patches of depigmentation. Zinc is an antiapoptotic molecule that exhibits antioxidant properties. The study aimed to investigate the serum levels of zinc in vitiligo patients compared to healthy controls and to whether exists a correlation between disease severity and serum levels of zinc. Fifty patients with vitilgo (group A) and 50 age and sex matched healthy controls (group B) were recruited and serum zinc level was measured using atomic absorption spectrophotometry and results were compared and correlated to each other and to disease severity and extension. The mean serum zinc levels in group A was 50.93 ± 11.02 in comparison to a mean of 77.09 ± 12.16 in group B (P = .049, T = -1.993). Vitiligo area severity index (VASI) scores in the vitiligo group ranged from 0.5 to 27 with a mean ± SD of (9.19 ± 4.47). A high statistically significant negative correlation was demonstrated between serum zinc levels and the extension of vitiligo (P value = .0001 and R value = - 0.835). A significant association exists between vitiligo and serum zinc levels. Serum zinc levels correlated negatively with vitiligo disease severity and extension. Zinc supplementation and use can be of potential importance in setting vitiligo treatment protocols.

Oxidative stress markers in neonatal respiratory distress syndrome: advanced oxidation protein products and 8-hydroxy-2-deoxyguanosine in relation to disease severity.

OBJECTIVE: We assessed oxidant-antioxidant status and evaluated the role of lipid peroxidation, oxidative DNA damage, and protein oxidation in the development and severity of neonatal respiratory distress syndrome (RDS). METHODS: Forty preterm neonates with RDS were compared with another 40 preterm neonates without RDS enrolled as controls. Total antioxidant capacity (TAC), malondialdehyde (MDA), advanced oxidation protein products (AOPPs), 8-hydroxy-2-deoxyguanosine (8-OHdG), and trace elements (copper and zinc) were measured in cord blood (day 0) for all neonates and repeated on day 3 for the RDS group. RESULTS: Day 0 serum levels of MDA, AOPPs, and 8-OHdG were significantly higher in neonates with RDS than controls with a further increase on day 3. Days 0 and 3 levels of TAC, copper, and zinc were significantly lower in the RDS group compared with controls. Elevated serum levels of 8-OHdG and AOPPs were associated with severe RDS, invasive mechanical ventilation, and high mortality rate. 8-OHdG and AOPPs were positively correlated with MDA, oxygenation index, duration of ventilation, and duration of hospitalization. CONCLUSIONS: Increased lipid, protein, and DNA oxidation is accompanied by alterations in the antioxidant defense status, which may play a role in the pathogenesis and severity of RDS.

The potential effect of methylseleninic acid (MSA) against γ-irradiation induced testicular damage in rats: Impact on JAK/STAT pathway.

This study suggested that methylseleninic acid (MSA) could respond to the inflammatory signaling associated with ionizing radiation-induced testicular damage. Mature male rats were divided into four groups: negative control, whole body γ-irradiated (IRR) (5 Gy), MSA (0.5 mg/kg, daily for nine consecutive days), and MSA+ IRR groups. MSA increased serum testosterone level and testicular glutathione peroxidase (GPx) as well as decreased the percentage of sperm abnormalities. Radiation prompted inflammatory signaling in the testes through increasing phospho-janus kinase1 (p-JAK1), phospho-signal transducers and activators of transcription 3 (p-STAT3) protein expressions. This induced increment in the inflammatory markers including nuclear factor- kappa B (NF-κB) and interleukin-1beta (IL-1ß) levels. Also, radiation induced elevation of nitric oxide (NO) and malondialdhyde (MDA) levels with consequent reduction in testicular reduced glutathione level (GSH) and superoxide dismutase (SOD) activity. MSA significantly counteracted the radiation effect on testicular nuclear factor erythroid-2-related factor-2 (Nrf2) and suppressor of cytokine signaling (Socs3) protein expressions. In summary, this investigation proposed that MSA preserved spermatogenesis through increasing testosterone levels and GPx activity. Additionally, it diminished testicular inflammation by increasing of Nrf2 and Socs3 levels leading to reducing of p-JAK1, p-STAT3 and NF-κB levels. Histopathological examination results of testicular tissues showed a coincidence with the biochemical analysis.

Effect of phototherapy on oxidant/antioxidant status: a randomized controlled trial.

In order to evaluate the effect of different types of phototherapy on oxidant/antioxidant status in hyperbilirubinemic neonates, an interventional randomized control trial was conducted on 120 neonates ≥35 weeks' gestational age with indirect hyperbilirubinemia reaching phototherapy level. This study is registered with ClinicalTrials.gov as NCT03074292. Neonates were assigned to three groups; 40 neonates received conventional phototherapy, 40 received intensive phototherapy and 40 received blue light-emitting diodes (LED) phototherapy. Complete blood count (CBC), total serum bilirubin (TSB), total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), copper (Cu), zinc (Zn), and iron (Fe) levels were measured before and 24 hours after phototherapy. TSB decreased postphototherapy in all three groups (p < .05 for all), with significantly lower levels following intensive and LED phototherapy compared to conventional phototherapy (p < .05 for both). TAC decreased postphototherapy in the three groups (p < .05 for all). MDA and NO increased postphototherapy (p < .05 for all), with the intensive phototherapy group having the highest levels followed by the conventional while LED phototherapy group showed the lowest levels in comparison to the other groups (p < .05). Cu, Zn and Fe increased postphototherapy in all three groups (p < .05 for all). Positive correlations were found between postphototherapy TSB with TAC, Cu and Zn (p < .05) and negative correlations with MDA, NO and Fe (p < .05) among neonates of the 3 studied groups. In conclusion, different photo therapies have an impact on oxidant/antioxidant balance and are associated with increased oxidative stress markers with the LED phototherapy being the safest.

Possible protective effect of the algae spirulina against nephrotoxicity induced by cyclosporine A and/or gamma radiation in rats.

The present study was conducted to evaluate the possible protective role of the algae spirulina (Sp) against nephrotoxicity and oxidative stress which are the main secondary effects induced by the immunosuppressant drug CSA and/or ionizing radiation. In this study, male rats were given Sp (1 g/kg) either for 15 days before irradiation (6.5 Gy) or 5 days before and 10 days concomitant with CSA (25 mg/kg). Markers used to assess renal injury included serum creatinine, urea, glucose, albumin, protein, and lipid profile as well as kidney content of reduced glutathione (GSH); lipid peroxidation (thiobarbituric acid reactive substances (TBARS)); nitrite and superoxide dismutase (SOD) activity. In addition, some trace elements (Zn and Mg) were estimated in kidney. Apoptosis was assessed by immunohistochemical estimation of caspase-3 expression in addition to histopathological examination. Results revealed that gamma radiation and/or CSA induced elevation in urea, creatinine, lipids, and glucose while decreasing albumin and protein levels. There was a noticeable increase in kidney content of GSH, TBARS, and nitrite. Meanwhile, profound decrease in kidney SOD activity was observed. Treatment with Sp significantly reversed the changes induced by CSA and/or gamma radiation in renal function tests. Spirulina also ameliorated kidney oxidative stress through decreasing GSH, TBARS, and nitrite kidney content while increasing SOD activity. Histopathological examination further confirmed Sp protective efficacy. Moreover, kidney caspase-3 expression that was triggered by CSA and/or gamma radiation was decreased. In conclusion, spirulina can be regarded as a promising renoprotective natural agent against renal injury induced by CSA and/or gamma radiation.

Ferulic acid protects against radiation-induced testicular damage in male rats: impact on SIRT1 and PARP1.

Ionizing radiation is a major contributor to male infertility by destroying spermatogenesis. Therefore, the need for an effective radio-protective agent is evident. The objective of the present study was to investigate the potential radio-protective effect of ferulic acid (FA) on radiation-induced testicular damage. Mature male Sprague-Dawley rats were either exposed to a single-dose gamma radiation (5 Gy) and/or treated with FA (50 mg/kg), daily for 7 days before irradiation. Sirtuin1 (SIRT1), poly (ADP-ribose) polymerase 1 (PARP1), cytosolic calcium content, and the male reproductive functions (sperm head abnormality) as well as oxidative stress markers were assessed 7 days after irradiation. FA significantly maintained active spermatogenesis. Moreover, it reversed the oxidative stress effects of irradiation. The irradiated group showed marked elevation in both PARP1 expression and activity as well as in cytosolic calcium concentration, whereas SIRT1 activity and expression markedly decreased; in contrast, FA treatment prevented these alterations. Results of histopathological examination of testicular tissues indicated coincidence with those recorded by biochemical analyses. Our data show for the first time that FA had radio-protective effect against radiation-induced testicular damage. It improved spermatogenesis through increasing testicular SIRT1 and testosterone levels and decreasing oxidative stress, PARP1, and cytosolic calcium.

Growth Hormone Ameliorates the Radiotherapy-Induced Ovarian Follicular Loss in Rats: Impact on Oxidative Stress, Apoptosis and IGF-1/IGF-1R Axis.

Radiotherapy is one of the standard cytotoxic therapies for cancer. However, it has a profound impact on ovarian function leading to premature ovarian failure and infertility. Since none of the currently available methods for fertility preservation guarantees future fertility, the need for an effective radioprotective agent is highly intensified. The present study investigated the mechanisms of the potential radioprotective effect of growth hormone (GH) on γ irradiation-induced ovarian failure and the impact of the insulin like growth factor 1 (IGF-1) in the underlying protection. Immature female Sprague-Dawley rats were either exposed to single whole body irradiation (3.2 Gy) and/or treated with GH (1 mg/kg s.c). Experimental γ-irradiation produced an array of ovarian dysfunction that was evident by assessment of hormonal changes, follicular development, proliferation marker (PCNA), oxidative stress as well as apoptotic markers. In addition, IGF-1/IGF-1R axis expression was assessed using real-time PCR and immunolocalization techniques. Furthermore, after full maturity, fertility assessment was performed. GH significantly enhanced follicular development and restored anti-Mullerian hormone serum level as compared with the irradiated group. In addition, GH significantly ameliorated the deleterious effects of irradiation on oxidative status, PCNA and apoptosis. Interestingly, GH was shown to enhance the ovarian IGF-1 at transcription and translation levels, a property that contributes significantly to its radioprotective effect. Finally, GH regained the fertility that was lost following irradiation. In conclusion, GH showed a radioprotective effect and rescued the ovarian reserve through increasing local IGF-1 level and counteracting the oxidative stress-mediated apoptosis.

Renal functional and structural integrity in infants with iron deficiency anemia: relation to oxidative stress and response to iron therapy.

BACKGROUND: Iron deficiency anemia (IDA) is the most common nutritional deficiency in the world. The aim of our study was to evaluate and compare renal functional and structural integrity in 50 infants with IDA and 50 healthy controls and to assess the relation between IDA and oxidative stress and response to iron therapy. METHODS: This was a prospective study in which peripheral blood samples were collected from all study subjects and the following laboratory investigations performed: serum iron profile, urinary microalbumin, urinary leucine aminopeptidase (LAP), fractional excretion of sodium (FeNa), serum total antioxidant capacity (TAC), serum malondialdehyde (MDA), serum and urinary trace elements (iron, copper, zinc, calcium and magnesium). All patients received oral iron therapy and were followed-up for 3 months. RESULTS: The levels of baseline urinary markers were higher among the patients with IDA than among the controls (p < 0.05). Patients had a lower pre-therapy TAC and lower serum zinc and magnesium levels than controls as well as higher MDA and serum copper levels (p < 0.05). MDA level was positively correlated to microalbumin and LAP level (p < 0.05). Urinary LAP concentration was positively correlated to urinary trace element concentrations (p < 0.05). A significant decrease in microalbumin, LAP, FeNa, and urinary trace elements was observed post-iron therapy while hemoglobin and ferritin levels were increased (p < 0.05). CONCLUSION: Among the study subjects, IDA had an adverse influence on renal functional and structural integrity which could be reversed with iron therapy. Oxidative stress played an important role in the pathogenesis of renal injury in IDA.

Insights into the protective mechanisms of tamoxifen in radiotherapy-induced ovarian follicular loss: impact on insulin-like growth factor 1.

Radiotherapy is one of the most common and effective cancer treatments. However, it has a profound impact on ovarian function, leading to premature ovarian failure. With the hope of preserving fertility in cancer survivors, the need for an effective radioprotective therapy is evident. The present study investigated the mechanism of the potential radioprotective effect of tamoxifen (TAM) on γ-irradiation-induced ovarian failure on experimental rats and the impact of the IGF-1 in the underlying protective mechanisms. Female Sprague Dawley rats were either exposed to single whole-body irradiation (3.2 Gy; lethal dose [LD20]) and/or treated with TAM (1 mg/kg). γ-Irradiation caused an array of ovarian dysfunction that was evident by assessment of hormonal changes, follicular development, proliferation marker (proliferating cell nuclear antigen), and oxidative stress as well as apoptotic markers. In addition, IGF-1/IGF-1 receptor axis expression was assessed using real-time RT-PCR and immunolocalization techniques. Furthermore, fertility assessment was performed. TAM significantly enhanced follicular development and restored the anti-Mullerian hormone level. Moreover, it ameliorated the deleterious effects of irradiation on oxidative stress, proliferating cell nuclear antigen expression, and apoptosis. Interestingly, TAM was shown to enhance the ovarian IGF-1 but not IGF-1 receptor, a property that contributed significantly to its radioprotective mechanisms. Finally, TAM regained the fertility that was lost after irradiation. In conclusion, TAM showed a radioprotective effect and saved the ovarian reserve and fertility through increasing anti-Mullerian hormone and the local IGF-1 level and counteracting the oxidative stress-mediated apoptosis.

Sodium selenite improves folliculogenesis in radiation-induced ovarian failure: a mechanistic approach.

Radiotherapy is a major factor contributing to female infertility by inducing premature ovarian failure (POF). Therefore, the need for an effective radioprotective agent is evident. The present study investigated the mechanism of potential radioprotective effect of sodium selenite on radiation-induced ovarian failure and whether sodium selenite can stimulate in-vivo follicular development in experimental rats. Immature female Sprague-Dawely rats were either exposed to gamma-radiation (3.2 Gy, LD(20)), once and/or treated with sodium selenite (0.5 mg/kg), once daily for one week before irradiation. Follicular and oocyte development, apoptotic markers, proliferation marker as well as oxidative stress markers were assessed 24-h after irradiation. In addition, fertility assessment was performed after female rats became completely mature at two months of age. Sodium selenite significantly enhanced follicular development as compared to the irradiated group. Sodium selenite significantly reversed the oxidative stress effects of radiation that was evidenced by increasing in lipid peroxide level and decreasing in glutathione level, and glutathione peroxidase (GPx) activity. Assessment of apoptosis and cell proliferation markers revealed that caspase 3 and cytochrome c expressions markedly-increased, whereas, PCNA expression markedly-decreased in the irradiated group; in contrast, sodium selenite treatment prevented these alterations. Histopathological examination further confirmed the radioprotective efficacy of sodium selenite and its in-vivo effect on ovarian follicles' maturation. In conclusion, sodium selenite showed a radioprotective effect and improved folliculogenesis through increasing ovarian granulosa cells proliferation, estradiol and FSH secretion, and GPx activity, whilst decreasing lipid peroxidation and oxidative stress, leading to inhibition of the apoptosis pathway through decreasing the expressions of caspase 3 and cytochrome c.

Radioprotective effect of Curcuma longa extract on γ-irradiation-induced oxidative stress in rats.

This study was conducted to evaluate the modulatory effect of aqueous extract of Curcuma longa (L.) against γ-irradiation (GR), which induces biochemical disorders in male rats. The sublethal dose of GR was determined in primary hepatocytes. Also, the effect of C. longa extract was examined for its activity against GR. In rats, C. longa extract was administered daily (200 mg/kg body mass) for 21 days before, and 7 days after GR exposure (6.5 Gy). The lipid profile and antioxidant status, as well as levels of transaminases, interleukin-6 (IL-6), and tumour necrosis factor α (TNFα) were assessed. The results showed that in hepatocytes, the aqueous extract exhibited radioprotective activity against exposure to GR. Exposure of untreated rats to GR resulted in transaminase disorders, lipid abnormalities, elevation of lipid peroxidation, trace element alterations, release of IL-6 and TNF, and decrease in glutathione and protein level of superoxide dismutase-1 (SOD-1) and peroxiredoxin-1 (PRDX-1). However, treatment of rats with this extract before and after GR exposure improved antioxidant status and minimized the radiation-induced increase in inflammatory cytokines. Changes occurred in the tissue levels of trace elements, and the protein levels of SOD-1 and PRDX-1 were also modulated by C. longa extract. Overall, C. longa exerted a beneficial radioprotective effect against radiation-induced oxidative stress in male rats by alleviating pathological disorders and modulating antioxidant enzymes.

Effect of selective COX-2 inhibitor, celecoxib on adjuvant-induced arthritis model in irradiated rats.

PURPOSE: The potential value of celecoxib was compared to a standard non-steroidal anti-inflammatory drug (NSAID), diclofenac in the adjuvant-induced arthritis (AIA) model in rats as a model of chronic inflammation under the influence of ionising radiation. MATERIAL AND METHODS: Various inflammatory mediators and biochemical parameters were measured in the arthritic rats under the influence of ionising radiation. RESULTS: Exposure of the animals to a radiation dose of 2 Gy before inoculation of the adjuvant led to a marked increase in the paw volume reaching ca. 70% more than that in non-irradiated ones as well as a significant increase in the levels of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α), prostaglandin E2 (PGE2) as an index of cyclooxygenase-2 (COX-2) activity, thromboxane B2 (TXB2) as an index of cyclooxygenase-1 (COX-1) activity and plasma level of malondialdehyde (MDA). The blood glutathione (GSH) level was not affected by the dose of irradiation used while superoxidedismutase (SOD) activity was reduced. Treatment with celecoxib in a dose of 5 mg/kg was effective in decreasing the elevated levels of IL-6, IL-1ß, TNF-α, PGE2 whereas it lacked any effect on TXB2 level since it had hardly any effect on COX-1 enzyme. Both drugs at the selected dose levels showed no effect on level of MDA, GSH and SOD activity. CONCLUSION: Irradiation of animals caused a marked change in the inflammatory response in AIA model of inflammation. Both celecoxib and diclofenac were nearly equipotent in suppressing the inflammatory response in both normal and irradiated rats. Accordingly, since the inhibition of COX-1 by traditional NSAID is thought to have undesirable side-effects on proliferating tissues, it would seem preferable to use selective COX-2 inhibitors to limit such deleterious effect.