Silymarin, the antioxidant component of Silybum marianum, protects against burn-induced oxidative skin injury

BACKGROUND: Despite recent advances, severe burn is one of the most common problems faced in the emergency room. Major thermal injury induces the activation of an inflammatory cascade resulting in local tissue damage, to contribute to the development of subsequent damage of multiple organs distant from the original burn wound. OBJECTIVE: Silymarin, the major component of milk thistle has been shown to have antioxidant properties. In the present study, we investigated the putative antioxidant effect of local or systemic silymarin treatment on burn-induced oxidative tissue injury. METHODS: Wistar albino rats were exposed to 90 degrees C bath for 10 s to induce burn. Silymarin either locally (30 mg/kg) applied on 4 cm(2) area or locally+systemically (50 mg/kg, p.o.) was administered after the burn and repeated twice daily. Rats were decapitated 48 h after injury and blood was collected for tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) activity. In skin tissue samples malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and luminol-lucigenin chemiluminescense (CL) were measured in addition to the histological evaluation. RESULTS: Burn caused a significant increase in TNF-alpha and LDH levels. MDA levels were increased and GSH levels were decreased in the skin at 48 h after-burn. Both local and systemic silymarin treatments significantly reversed these parameters. The raised MPO activity and luminol-lucigenin CL were also significantly decreased. CONCLUSION: Results indicate that both systemic and local administration of silymarin was effective against burn-induced oxidative damage and morphological alterations in rat skin. Therefore, silymarin merits consideration as a therapeutic agent in the treatment of burns.     

Hypertonic saline resuscitation protects against kidney injury induced by severe burns in rats

BackgroundProper fluid resuscitation can relieve visceral damage and improve survival in severely burned patients. This study compared the effectiveness of resuscitation with 400 mEq/L hypertonic saline (HS) and sodium lactate Ringer’s solution (LR) in rats with kidney injury caused by burn trauma.MethodsRats (Sprague-Dawley) underwent burn injury and were randomized into sham, LR, and HS groups. Samples from the kidney were assayed for water content ratio, histopathology, and oxidative stress (superoxide dismutase (SOD) and malondialdehyde (MDA)). Serum sodium, renal function (creatinine and cystatin (Cys)-C), and inflammatory response (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and high mobility group protein box (HMGB)-1) were also examined as serum markers.ResultsHypertonic saline resuscitation reduced the renal water content ratio and improved renal histopathology caused by severe burns. This effect was accompanied by reductions in serum creatinine and Cys-C as well as TNF-α, IL-1β, and HMGB1. Serum sodium concentration and SOD activity were increased, whereas MDA content was decreased in the kidney tissue of the HS group.ConclusionsThe data indicate that 400 mEq/L HS solution reduces hyponatremia and renal edema, inhibits the release of inflammatory mediators, and alleviates oxidative stress injury, thus protecting against kidney injury induced by severe burns.     

Propylthiouracil (PTU)-induced hypothyroidism alleviates burn-induced multiple organ injury

Oxidative stress has an important role in the development of multiorgan failure after major burn. This study was designed to determine the possible protective effect of experimental hypothyroidism in hepatic and gastrointestinal injury induced by thermal trauma. Sprague Dawley rats were administered saline or PTU (10 mgkg(-1) i.p.) for 15 days, and hypothyroidism was confirmed by depressed serum T(3) and T(4) concentrations. Under brief ether anesthesia, shaved dorsum of rats was exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10s. PTU or saline treatment was repeated at the 12th hour of the burn. Rats were decapitated 24h after injury and tissue samples from liver, stomach and ileum were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Formation of reactive oxygen species in tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Tissues were also examined microscopically. Tumor necrosis factor (TNF)-alpha and lactate dehydrogenase (LDH) were assayed in serum samples. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity, CL levels and collagen content of the studied tissues (p<0.05-0.001). Similarly, serum TNF-alpha and LDH were elevated in the burn group as compared to control group. On the other hand, PTU treatment reversed all these biochemical indices, as well as histopathological alterations induced by thermal trauma. Our results suggest that PTU-induced hypothyroidism reduces oxidative damage in the hepatic, gastric and ileal tissues probably due to hypometabolism, which is associated with decreased production of reactive oxygen metabolites and enhancement of antioxidant mechanisms.     

Clostridial collagenase aggravates the systemic inflammatory response in rats with partial-thickness burns

AimClostridial collagenase A (CCA) has been shown effective in degrading collagen in eschar tissue and promoting healing in partial-thickness burns. As there are also reports of fever, leukocytosis, increased C-reactive protein (CRP) levels and septic complications during treatment with CCA, we aimed to determine in rats whether CCA aggravates the systemic inflammatory response.MethodsRats with partial-thickness burns were randomly divided into groups with either no dressing (ND), povidone-iodine dressing (PID) or CCA dressing (CCAD). Body weights and temperatures, blood leukocyte counts, and serum levels of CRP, interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α), were measured at 0, 3, and 24 h and days 3 and 7 from burn. Wounds were cultured on days 1, 3 and 7 and burn depth was evaluated on day 1.ResultsBody weights for all groups were significantly lower after burn, with highest loss (25.5%) in the CCAD group. At 3 h a significant drop in rectal temperature was noted in all groups. The CCAD group had higher rectal temperature levels than the PID group on days 3 and 7 (p < 0.05). Changes in serum levels of CRP, IL-1β, IL-6 and TNF-α were not significant in the ND and PID groups; the CCAD group showed a significant rise in serum levels of CRP on day 1, of IL-6 on day 3 and of TNF-α on day 7. Wound infection was more common in CCAD group and increased on days 3 and 7, but this was insignificant.ConclusionCCA aggravated the systemic inflammatory response in rats with partial-thickness burns, which is accompanied by a higher risk of infection.     

Effects of high-voltage electrical burns and other burns on levels of serum oxidative stress and telomerase in children

Introduction

Electrical burns cause significant morbidity and mortality worldwide. Here we measured changes in levels of serum oxidative stress and telomerase in children suffering from high-voltage electrical burn (HVEB) injuries and other burns and the significance of these parameters in terms of amputation.

Resistin forms a network with inflammatory cytokines and is associated with prognosis in major burns

BackgroundIn current intensive care treatment, some patients with severe burns cannot be saved due to progressive organ failure. Further investigation of the pathogenesis of severe burns is needed to improve the mortality rate. In burns, inflammatory cytokines form a network that leads to an inflammatory response. Adipocytes secrete physiologically active substances (adipokines). The roles of adipokines have not been completely clarified in burn patients. This study aimed to determine the relation between serial changes of adipokines and clinical course in severely burned patients.MethodsThis was a single-center, retrospective, observational study. Patients’ blood samples were collected on the day of injury and around 1 week later. Adipokines (adiponectin, angiotensinogen, chemerin, CXCL-12/SDF-1, leptin, resistin, vaspin, visfatin), various inflammatory cytokines, syndecan-1 and C1 esterase inhibitor were measured.ResultsThirty-eight patients were included. Resistin levels were significantly higher in the non-survivors versus survivors on Day 1 after burn injury. Hierarchical clustering analysis showed common clusters on Day 1 and at 1 Week after burn injury (resistin, IL-6, IL-8, IL10 and MCP-1). The correlation coefficient of resistin to SOFA score at 1 Week was significant. Logistic regression analysis showed a significant relation of resistin levels on Day 1 with prognosis; the area under the ROC curve for resistin was 0.801.ConclusionsIn the acute phase of burns, resistin was associated with other pro-inflammatory cytokines and was related to the severity and prognosis of major burns.     

Multicentre observational study describing the systemic response to small-area burns in children

Background and ObjectivesBurns of less than 10% total body surface area (TBSA) are common injuries in children under five years of age. The inflammatory response to burn injury is well recognised for burns greater than 20% TBSA but has not been described for smaller burns. The aim of this study was to describe the systemic response to burn injury in young children with small-area burns.MethodsThe Morbidity In Small Thermal Injury in Children study (MISTIC) was a multicentre prospective observational cohort study that recruited 625 patients under five years of age with burns of less than 10% TBSA over eighteen months across three sites in England. Prospectively collected data included physical observations and laboratory blood tests taken in hospital as part of routine care. Additional information was sourced from temperature recordings taken at home following discharge.ResultsElevated temperatures were observed in children with scald or contact burns between 2–10% TBSA, with a peak on day one after burn followed by a fall over days four to seven after burn. No temperature rise was seen in children with burns of <2% TBSA. Higher temperature readings were associated with larger burn size, age under two years and male sex. Heart rate and C-Reactive Protein levels showed a peak on day three after burn.ConclusionsAn identifiable systemic inflammatory response to small-area burns in young children is reported. This knowledge can be used to aid in the diagnosis of children with a burn injury who re-present with a pyrexia, and no other symptoms to indicate clinical infection.     

Sodium butyrate inhibits the production of HMGB1 and attenuates severe burn plus delayed resuscitation-induced intestine injury via the p38 signaling pathway

BackgroundInflammatory response triggered by high mobility group box-1 (HMGB1) protein and oxidative stress play critical roles in the intestinal injury after severe burn. Sodium butyrate, a histone deacetylase inhibitor, has potential anti-inflammatory properties, inhibiting the expression of inflammatory mediators such as HMGB1 in diverse diseases. This study was designed to investigate the effects of sodium butyrate on severe burn plus delayed resuscitation-induced intestine injury, intestinal expressions of HMGB1 and intracellular adhesion molecule-1 (ICAM-1), oxidative stress, and signal transduction pathway changes in rats.Materials and methodsFifty-six Sprague-Dawley rats were divided into 3 groups randomly: (1) sham group, animals underwent sham burn; (2) burn group, rats subjected to full-thickness burns of 30% total body surface area (TBSA) and received 2 ml/kg/TBSA lactated Ringer solution for resuscitation at 6, 12, and 36 h after burn injury; (3) burn plus sodium butyrate (burn + SB) group, animals received burn injury and lactated Ringer solution with sodium butyrate inside for resuscitation in the same manner. Diamine oxidase (DAO) concentration in plasma was measured by enzyme-linked immunosorbent assay. Intestinal fatty acid binding protein (I-FABP) and ICAM-1 expressions in the intestine were analyzed by immunohistochemical method. HMGB1 and p38 mitogen-activated protein kinase (MAPK) expressions in the intestine tissues were examined by Western blot. The intestinal concentration of malondialdehyde (MDA) was also determined.ResultsIntestinal HMGB1 expression was significantly increased in burn group compared with sham group. Sodium butyrate administration significantly inhibited the HMGB1 expression in the intestine, decreased the DAO concentration in plasma, reduced the intestinal I-FABP expression, and improved the intestinal histologic changes induced by burn injury plus delayed resuscitation. Sodium butyrate treatment also markedly reduced the increase of intestinal ICAM-1 expression and MDA content, and inhibited p38 MAPK activity in the intestine of severely burned rats with delayed resuscitation.ConclusionsSodium butyrate inhibits HMGB1 expression which could be attributed to p38 MAPK signal transduction pathway and decreases intestinal inflammatory responses and oxidative stress, thus attenuates burn plus delayed resuscitation-induced intestine injury.     

Lycopene has reduced renal damage histopathologically and biochemically in experimental renal ischemia-reperfusion injury

Abstract

Background: The present study aimed to investigate whether the inflammatory and antioxidant lycopene has a therapeutic effect against renal ischemia/reperfusion (I/R) injury. Materials and methods: In this study, 24 Wistar-Albino rats, weighing from 200 to 250?g, were divided into four groups. All rats underwent median laparotomy under anesthesia. No procedures were performed in the control group (Group C), whereas 100?mg/kg lycopene was administered by gavage in the lycopene group (Group L). The arteries of both kidneys were clamped for 45?min in the ischemia group (Group I), whereas 100?mg/kg lycopene was administered by gavage 30?min before clamping renal arteries, and ischemia was performed in the treatment group (Group T) rats. For all rats, blood samples and renal tissues were collected at 6?h of reperfusion. Samples were used to examine serum BUN, creatinine, MDA and GSH levels, and the renal tissues were used to examine MDA and GSH levels, and renal histopathologies. Results: The treatment group had statistically significant lower serum MDA levels, histopathological tubular vacuolization, loss of brush border and tubular dilatation (p?<?0.05), whereas serum BUN, creatinine, tissue MDA, and tissue and serum GSH levels were improved in favor of the treatment group, even though it was not statistically significant (p?>?0.05). Conclusion: The present study demonstrated that lycopene, which was administered prior to renal I/R injury, prevented renal damage through biochemical and histopathological parameters.     

Does metronidazole reduce lipid peroxidation in burn injuries to promote healing?

In our earlier study metronidazole, administered orally, promoted healing in partial thickness burn wounds. This prompted us to hypothesize that metronidazole might have influenced lipid peroxidation, since increased levels of lipid peroxide are seen in burn injuries. Thus, the present study was aimed at investigating if metronidazole had any antioxidant action in burned rats.The effects of metronidazole and antioxidants (Vitamins E and C) were assessed on the serum malondialdehyde (MDA) levels and on epithelization in partial thickness burned-wound rats.Metronidazole and antioxidants significantly reduced the increased serum MDA levels in the 48h post burn. They also significantly hastened the epithelization process. The results suggest a line between ends of oxidative products and rate of epithelization.Metronidazole, if administered to patients with burns, besides offering protection against anaerobic infections, might also protect the patients from some aspects of burn induced oxidative stress.     

Enzymatic debridement in critically injured burn patients — Our experience in the intensive care setting and during burn resuscitation

BackgroundMuch of the recent literature on bromelain based enzymatic debridement of burn injury has focused on its use in smaller burn injury and specialist areas such as the hands or genitals (Krieger et al., 2012; Schulz et al., 2017a,b,c,d). This is despite the original papers describing its use in larger burn injury (Rosenberg et al., 2004, 2014).The current EMA license for Nexobrid? advises that it should not be used for burn injuries of more than 15% TBSA and should be used with caution in patients with pulmonary burn trauma and suspected pulmonary burn trauma. The original safety and efficacy trial of NexoBrid? limited its use to 15% TBSA aliquots with concern regarding the effect of bromelain on coagulation. In a European consensus paper of experienced burns clinicians, now on its second iteration, 100% of respondents agreed that “up to 30% BSA can be treated by enzymatic debridement based on individual decision” (Hirche et al., 2017). Hofmaenner et al.’s recent study on the safety of enzymatic debridement in extensive burns larger than 15% provides some further evidence that “bromelain based enzymatic debridement can be carried out safely in large-area burns” (Hofmaenner et al., 2020) but the literature is scant in these larger debridement areas.In our centre we have been using enzymatic debridement for resuscitation level burn injury since 2016. We have gained significant learning in this time; this article aims to describe our current protocol for enzymatic debridement in this patient population and highlight specific learning points that might aid other centres in using enzymatic debridement for larger burn injury.MethodWe performed a search of the IBID database to identify all adult patients who satisfied the inclusion criteria of resuscitation level burn injury (defined as total burn surface area (TBSA) ≥15% in patients aged >16 years), or level 3 admission following burn injury and who underwent Enzymatic Debridement. A case note review was completed, and details comprising patient demographics, TBSA, mechanism of burn, presence of inhalation injury, sequencing of debridement, length of ICU and hospital stay, blood product utilisation and the need for autografting were recorded. No ethical approval has been sought for this retrospective review.ResultsWe identified 29 patients satisfying the inclusion criteria (Table 1). Between June 2016 and June 2020 the average total burn size of patients who had at least some of their burn treated by enzymatic debridement increased from 21.4% in 2016/17 to 34.7% in 2019/20. In these patients the actual area treated by enzymatic debridement also increased from 11.9% TBSA to 20.3% TBSA. 19 patients (66%) had enzymatic debridement performed within 24 h of injury, a further 2 patients (7%) within 48 h after injury. Patients were more likely to have enzymatic debridement commenced in the first 24 h after injury if they had circumferential limb injury (39% vs 9%) or were planned for enzyme only debridement (78% vs 28%). Those who were planned for combination enzyme and surgical debridement were more likely to have enzymatic debridement commenced after the first 48 h (75%). We have performed enzymatic debridement overnight on one occasion, for a patient who presented with circumferential limb injury and was determined to undergo urgent debridement.ConclusionMuch of the literature has described the use of enzymatic debridement in smaller burns, and specialist areas. However, it is our opinion that the advantages of enzymatic debridement appear to be greater in larger burns with a facility for whole burn excision on the day of admission in the ICU cubicle. We have demonstrated significantly reduced blood loss, improved dermal preservation, reduced need for autografting, and a reduction in the number of trips to theatre. We would advocate that both the team and the patient need to be as prepared as they would be for a traditional surgical excision. The early part of our learning curve for enzymatic debridement in resuscitation level injuries was steep, and we were able to build on experience from managing smaller injuries. We recommend any team wishing to using enzymatic debridement gain experience in the same way and develop robust local pathways prior to attempting use in larger burn injuries.     

Effects of topical application of platelet-rich plasma on esophageal stricture and oxidative stress after caustic burn in rats: Is autologous treatment possible?

BackgroundCaustic esophageal burn is still an important health problem in pediatric surgery. Although there are a number of experimental and clinical studies to increase the recovery of the esophagus and reduce the stenosis rate, there is no consensus on the treatment protocol. Platelet-rich plasma (PRP) is an autologous blood product, which has positive effects on wound healing, reepithelization and scar prevention. The aim of our study was to investigate the effects of PRP on stricture formation and oxidative status after caustic esophageal injury in rats.MethodsTwenty-one rats were divided into three groups [Sham operation (n = 8), corrosive esophageal burn with 30% NaOH (n = 6), topical PRP application after corrosive burn (n = 7)]. On the postoperative 21st day, oxidative markers were measured in the serum, and collagen accumulation and stenosis index were measured histopathologically to assess the efficacy of PRP treatment.ResultsPostoperative weight was higher than preoperative weight in Sham and PRP groups, but lower in the Burn group (p < 0.05). No difference was observed between Sham and PRP groups at total antioxidant status and paraoxonase values, but a significant decrease was found in the Burn group. Group PRP had higher total oxidant status and arylesterase levels than Group Burn (p < 0.05). There was no difference in total thiol values between PRP and Sham group. Histopathological scoring for muscularis mucosa damage revealed a significant reduction in Group PRP, compared to Group Burn (p < 0.05). Esophageal wall thickness and SI were reduced, and luminal diameter was increased in Group PRP compared to Group Burn (p < 0.05).ConclusionFor the first time in the literature, these results indicate that topical PRP treatment after the experimental corrosive burn has a positive effect on oxidative stress, mucosal healing and decreased stricture development. PRP may be an alternative at the clinical treatment because it can be used during diagnostic esophagoscopy.Type of studyTreatment study Level I (randomized controlled trial).     

Mouse models in burns research: Characterisation of the hypermetabolic response to burn injury

ObjectiveThe aim of the study is to characterise burn induced hypermetabolism in a mouse model.Summary Background DataThere are many mouse models of burn injury currently available however, their use in burns research is limited by the general assumption that post-burn hypermetabolism is difficult to study in these models.MethodsMale Balb/c mice were subjected to either a small (1 cm²) or large (4 cm²) contact burn. The hypermetabolic response to burn injury was determined by measuring changes in basal energy expenditure. The hormonal and inflammatory mediators of hypermetabolism, and the catabolic alterations secondary to hypermetabolism were also examined.ResultsPost-burn hypermetabolism was induced in both models of small and large burn. However, large burns resulted in prolonged wound healing, a more pronounced and sustained increase in basal energy expenditure, and a greater stress and systemic inflammatory response with profound catabolic consequences.ConclusionsIn the present study, we have successfully characterised the burn induced systemic hypermetabolic response in a mouse model of small and large burn. These models may prove useful for researchers studying the complex aetiology of hypermetabolism and interventions.     

The effect of burn mechanism on pediatric mortality in Malawi: A propensity weighted analysis

IntroductionThe burden of global trauma disproportionately affects low- and middle-income countries, with a high incidence in children. Thermal injury represents one of the most severe forms of trauma and is associated with remarkable morbidity and mortality. The predictors of burn mortality have been well described (age, % total body surface area burn [TBSA], and presence of inhalation injury). However, the contribution of the burn mechanism as a predictor of burn mortality is not well delineated.MethodsThis is a retrospective analysis of prospectively collected data, utilizing the Kamuzu Central Hospital (KCH) Burn Surveillance Registry from May 2011 to August 2019. Pediatric patients (≤12 years) with flame and scald burns were included in the study. Basic demographic variables including sex, age, time to presentation, %TBSA, surgical intervention, burn mechanism, and in-hospital mortality outcome was collected. Bivariate analysis comparing demographic, burn characteristics, surgical intervention, and patient outcomes were performed. Standardized estimates were adjusted using inverse-probability of treatment weights (IPTW) to account for confounding. Following weighting, logistic regression modeling was performed to determine the odds of in-hospital mortality based on burn mechanism.ResultsDuring the study period, 2364 patients presented to KCH for burns and included in the database with 1794 (75.9%) pediatric patients. Of these, 488 (27.6%) and 1280 (72.4%) were injured by flame and scald burns, respectively. Males were 47.2% (n = 230) and 59.2% (n = 755) of the flame and scald burn cohorts, respectively (p < 0.001.) Patients presenting with flame burns compared to scald burns were older (4. 7 ± 3.1 vs. 2.7 ± 2.3 years, p < 0.001) with greater %TBSA burns (17.8 [IQR 10–28] vs 12 [IQR 7–20], p < 0.001). Surgery was performed for 42.2% (n = 206) and 19.9% (n = 140) of the flame and scald burn cohorts, respectively (p < 0.001.) Flame burns had a 2.6x greater odds of in-hospital mortality compared to scald burns (p < 0.001) after controlling for sex, %TBSA, age, time to presentation, and surgical status.ConclusionIn this propensity-weighted analysis, we show that burn mechanism, specifically flame burns, resulted in a nearly 3-fold increase in odds of in-hospital mortality compared to scald burns. Our results emphasize flame and scald burns have major differences in the inflammatory response, metabolic profile over time, and outcomes. We may further utilize these differences to develop specialized treatments for each burn mechanism to potentially prevent metabolic dysfunction and improve clinical outcomes.     

Effect of melatonin on burn-induced gastric mucosal injury in rats

We studied the effect of melatonin treatment on gastric mucosal damage induced by experimental burns and its possible relation to changes in gastric lipid peroxidation status. Melatonin was intraperitoneally applied immediately after third-degree burns over 30% of total body skin surface area of rats. Malondialdehyde (MDA), uric acid (UA) and sulphydril (SH) levels were determined in gastric mucosa and blood plasma and used as biomarkers of the oxidative stress. The results showed that the skin burn caused oxidative stress evidenced by accumulation of MDA and UA as well as the depletion of SHs in gastric mucosa. Plasma MDA concentrations were elevated, while plasma SH concentrations were decreased after burns. Melatonin (10 mg per kg body weight) protected gastric mucosa from oxidative damage by suppressing lipid peroxidation and activating the antioxidant defence. It may be hypothesised that melatonin restores the redox balance in the gastric mucosa and protects it from burn-induced oxidative injury. Melatonin has no significant influence on the concentrations of plasma MDA and antioxidants after burn; therefore, it should largely be considered as a limiting factor for tissue-damage.     

Berberine ameliorates experimental varicocele‐induced damages at testis and sperm levels; evidences for oxidative stress and inflammation

The present study was performed to show the ameliorative effect of berberine (BBR), as an antioxidant and anti‐inflammatory agent, against experimental varicocele (VCL)‐induced molecular and histological damages. For this purpose, 50 mature Wistar rats were divided into control, control‐sham, VCL‐sole, 50 mg/kg and 100 mg/kg BBR‐treated VCL‐induced groups. The tissue levels of interleukin‐6 (IL‐6), tumour necrosis factor‐α (TNF‐α), nitric oxide (NO), total antioxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD) and gluthatione peroxidase (GSH‐px) as well as the mRNA levels of testicular CuZn SOD, MnSOD, EC‐SOD and GSH‐px were evaluated. The serum concentration of testosterone and germ cells mRNA damage were analysed. Finally, the sperm viability, motility, DNA integrity and chromatin condensation were analysed. Observations revealed that, the BBR significantly downregulated VCL‐increased IL‐6, TNF‐α and NO levels, upregulated the CuZn SOD, MnSOD, EC‐SOD and GSH‐px mRNA level, decreased testicular MDA content, enhanced serum testosterone level and ameliorated testicular TAC, SOD and GSH‐px levels. The animals in BBR‐treated groups exhibited diminished mRNA damage versus non‐treated VCL‐induced group. The BBR has significantly (p < 0.05) improved sperm parameters. In conclusion, the BBR by promoting testicular antioxidant potential and by downregulating inflammatory reactions fairly promotes spermatogenesis and upregulates the sperm quality.     

Pretreatment with Pentoxifylline and N-Acetylcysteine in Liver Ischemia Reperfusion-Induced Renal Injury

Background and Aims: Acute hepatic injury causes systematic inflammatory responses which may finally lead to functional disturbances in remote organs. In this study, the effects of an inhibitor of inflammatory cytokines (pentoxifylline, PTX) and a well-known antioxidant, N-acetylcysteine (NAC), were evaluated on renal damage and oxidative stress following liver ischemia reperfusion (IR). Method: Five groups of six male rats were used. Group 1 was sham operated. In group 2, 90 min liver partial ischemia was induced by a clamp around both hepatic artery and portal vein and then followed by 4 h of reperfusion. In groups 3 and 4, PTX or NAC was injected intraperitoneally before the ischemia, while in group 5 both drugs were co-administered. The levels of alanine amino-transferase (ALT), aspartate amino-transferase (AST), blood urea nitrogen (BUN), and creatinine in serum as well as malonyldialdehyde (MDA) and glutathione (GSH) levels and morphological changes in renal tissues were assessed. Results: Significant increase in the serum levels of ALT and AST in IR group is indicative of liver functional damages. Elevated BUN and renal tissue MDA, decreased GSH levels, and morphological damages in IR group demonstrate a significant kidney injury and oxidative stress comparing to sham group. Administration of PTX alone and PTX + NAC prevented the IR-induced increase in renal MDA levels. Administration of both drugs and their co-administration prevented the reduction in renal GSH levels and morphological changes. Conclusion: Pretreatment with PTX and NAC before liver IR may be useful to ameliorate renal oxidative damage by preservation of cellular GSH concentration and a reduction in MDA levels.     

The effect of N-acetylcysteine on oxidative stress in intestine and bacterial translocation after thermal injury

Ischemia due to transient splanchnic vasoconstriction following major burns causes oxidative and/or nitrosative damage in intestinal tissue followed by reperfusion injury. Thus, burn injury leads to breakdown in the intestinal mucosal barrier which can induce bacterial translocation (BT). As an antioxidant and anti-inflammatory agent the protective effects of N-acetylcysteine (NAC) are documented in several studies. This study was designed to determine the effect of NAC treatment on the oxidative stress in the intestine and BT after burn injury. To evaluate this, 32 Wistar rats were randomly divided into four groups as sham (n = 8), burn (n = 8), pre-burn, NAC injection (150 mg kg⁻¹, intraperitoneally) 15 min before thermal injury (n = 8), post-burn, NAC injection (150 mg kg⁻¹, intraperitoneally) 2 h after thermal injury. Under anesthesia, the shaved dorsal skin of rats was exposed to boiling water for 12 s to induce burn injury in a standardized manner. Twenty-four hours later, tissue samples from mesenteric lymph nodes (MLN), spleen, and liver were obtained under sterile conditions for microbiological analysis and ileum samples were harvested for biochemical analysis. In the burn group, the incidence of isolating bacteria in MLN, spleen, and liver specimens was significantly higher than other groups. NAC treatment prevented burn-induced BT in both pre- and post-burn groups. Thermal injury caused a significant decrease in glutathione (GSH) level, significant increases in malondialdehyde (MDA) and myeloperoxidase (MPO) activity at post-burn 24th hour. Treatment of rats with NAC significantly elevated the reduced GSH levels while decreasing MDA levels and MPO activity. These data suggested that NAC has a crucial cytoprotective role in intestinal mucosal barrier and preventive effects against burn injury-induced BT.     

The effect of partial unilateral ureteral obstruction release and allopurinol on the renal malondialdehyde and glutathione levels

PURPOSE: The aim of the present study was to evaluate whether relief of partial unilateral ureteral obstruction (PUUO) with or without antioxidant drug affect renal tissue malonedialdehyde (MDA) and glutathion (GSH) levels. MATERIALS AND METHODS: A total of 25 rats were used in this PUUO study. Partial unilateral ureteral obstruction was created by the burial of the upper one-third of the left ureter in the psoas muscle. The rats were sacrificed on 28th day following PUUO. Relief of the obstruction was performed twenty minutes before sacrifice by cutting the proximal ureter in reperfusion group. 50 mg/kg intraperitoneal allopurinol was administered 20 minutes before relief of obstruction in the antioxidant group. Renal tissue MDA and GSH levels were measured in both kidneys. RESULTS: At the end of the study 5, 7 and 7 rats could only be interpreted in sham, reperfusion and antioxidant groups, respectively. While the mean left and right renal MDA and GSH levels were statistically different from each other in reperfusion group (P < 0.001), there were no significant differences in the sham (P > 0.05) and antioxidant (P > 0.05) group. Both the mean sham group left and right renal tissue MDA or GSH levels were significantly different from reperfusion group, but only the mean sham group left renal tissue MDA and right renal tissue GSH levels were not statistically different from antioxidant group (P < 0.05). The mean left or right renal MDA and GSH tissue levels of the antioxidant group were statistically different from reperfusion group (P < 0.05) except for the right renal tissue GSH level (P > 0.05). CONCLUSION: Partial unilateral ureteral obstruction leads to oxidative injury by relief of obstruction in both kidneys. The antioxidant allopurinol has a beneficial effect on renal MDA and GSH levels in both kidneys.