Dexmedetomidine alleviates vacuolization and necrosis in tubular epithelial cells induced by aortic cross-clamping.

OBJECTIVE: Acute kidney injury (AKI) is one of the main causes of mortality in patients undergoing emergency surgery due to an abdominal aortic aneurysm. This study aimed to determine the potential nephroprotective characteristics of dexmedetomidine (DMD) for the establishment of a standard therapeutic method for AKI. MATERIALS AND METHODS: Thirty Spraque Dawley rats were allocated to 4 groups: control, sham, ischemia-reperfusion, and ischemia/reperfusion (I/R)+dexmedatomidine. RESULTS: Necrotic tubules, degenerative Bowman's capsule and vascular congestion were observed in the I/R group. In addition, there was an increase in tissue malondialdehyde (MDA), interleukin (IL)-1 and IL-6 levels in tubular epithelial cells. In contrast, we observed decreased tubular necrosis, IL-1, IL-6 and MDA levels in the DMD treatment group. CONCLUSIONS: DMD has a nephroprotective effect against acute kidney injury resulting from I/R, which is related to aortic occlusion used in the treatment of ruptured abdominal aortic aneurysms.

The effects of dexmedetomidine on early acute kidney injury in severely burned rats.

OBJECTIVE: Burns are a global medical and economic problem. In addition to high costs, the lengthy therapeutic process and the emotional trauma experienced by patients and their families indirectly worsen the socioeconomic damage caused. Kidney failure observed after burns is highly correlated with mortality. MATERIALS AND METHODS: Twenty-eight male Sprague-Dawley rats (age four months, weight 250-350 g) were included in the study. They were randomly assigned into four groups consisting of seven rats each with similar mean weights. Group 1 (n=7) represented the healthy control group (C), Group 2 (n=7) the Sham+dexmedetomidine (DEX) 100 mcg/kg (three doses) (S+DEX100) group, Group 3 (n=7) the 30% Burn (B), and Group 4 (n=7) the 30% Burn+DEX 100 mcg/kg/day group (B+DEX100) (three doses). Thiobarbituric acid reactive substances (TBARS), total thiol (TT), interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) values in kidney tissues were investigated biochemically, and histopathological analyses were also performed. Nuclear factor κB (NF-κB)/p65 was measured using immunohistochemistry, and the TUNEL assay was applied to indicate apoptotic tubular epithelial cells. RESULTS: TBARS, IL-1, and TNF-α in kidney tissues decreased in the B+DEX100 group compared to the 30% burn group, while total thiol values increased. Histopathologically, atypical glomeruli, particularly necrotic tubules, and inflammation in peritubular areas decreased in the B+DEX100 group compared to the 30% burn group. In addition, apoptotic tubular epithelial cells exhibiting TUNEL positivity and tubular epithelial cells exhibiting NF-кß/p65 positivity also decreased in the B+DEX100 group compared to the 30% burn group. CONCLUSIONS: Dexmedetomidine reduced apoptotic activity in rats and exhibited anti-inflammatory antioxidant effects in the burn model in this study.

Radioprotective effects of dexmedetomidine on X-ray-induced testicular damage.

OBJECTIVE: Approximately 70% of cancer patients require radiotherapy. However, despite its effectiveness in the treatment of cancer, radiotherapy can also affect and damage surrounding healthy tissues in addition to tumorous tissues. Since testicular tissues are highly radiosensitive, radiotherapy can cause impairments in spermatogenesis leading to infertility. The purpose of this study was to examine the potential radio-protective effect of dexmedetomidine (Dex), an α2-adrenoceptor agonist, on oxidative stress and apoptosis in testicular tissues caused by x-irradiation in rats. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were allocated into three groups of ten (n=10): control, irradiation (IR), and IR + Dex groups. The IR group was exposed to a single dose of 2 Gy IR. The IR+Dex group was given a single intraperitoneal (i.p.) dose of 100 µg/kg Dex before IR. The control group received a single dose of saline solution i.p. Testicular tissues removed 24 hours after IR were subjected to histochemical, biochemical, and immunohistochemical analysis. RESULTS: IR resulted in increased malondialdehyde (MDA) activity and significant changes in testis tissues. However, the application of Dex elevated glutathione levels by preventing MDA formation. In addition, Dex decreased tubular epithelial apoptosis via elevated Cleaved Caspase-3 expressions. CONCLUSIONS: Dex exhibited a radio-protective effect against lipid peroxidation and apoptosis caused by IR.

Effects of infliximab against carbon tetrachloride-induced spleen toxicity in rats.

OBJECTIVE: Carbon tetrachloride (CCl4) is a non-polar molecule used in industry in grain curing, insect-killing and especially in the production of chlorofluorocarbons. It is estimated that an average of 70,000 industry workers in Europe are exposed to this toxic compound. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley rats were randomly allocated into four groups: control group (saline only, Group I), infliximab (INF) group (Group II), CCl4 group (Group III) and CCl4+INF group (Group IV). RESULTS: While there was an increase in the numerical density of CD3, CD68, and CD200R positive T lymphocytes and macrophages in the CCl4 administration group (p=0.000), this was not the case in the CCl4+INF administration group (p=0.000). CONCLUSIONS: TNF-α inhibitors have a protective effect against CCl4-induced spleen toxicity/inflammation as seen by the reduction in CD3, CD68, CD200R positive T lymphocytes and macrophages.

The nephroprotective effect of amifostine in a cecal ligation-induced sepsis model in terms of oxidative stress and inflammation.

OBJECTIVE: Sepsis is responsible for more than 5 million deaths worldwide every year. The purpose of this study was to use amifostine to reduce acute kidney injury developing as a result of sepsis. MATERIALS AND METHODS: Thirty Sprague Dawley rats were divided into three equal groups - a healthy control group (Group 1), cecal ligation and puncture group (CLP, Group 2), and a CLP + amifostine (AMF) group receiving a total of 200 mg/kg AMF intraperitoneally (i.p.) 15 min before sepsis induction (Group 3). RESULTS: Total thiol levels decreased while malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB/p65), and interleukin (IL)-1ß, and IL-6 levels increased in the CLP group. We also observed degeneration in renal corpuscles, necrotic tubules, polymorphonuclear leukocyte inflammation, and vascular congestion. In the amifostine group, total thiol levels in tissue increased, while MDA, TNF-α, NF-кB/p65, IL-1ß, and IL-6 levels, necrotic renal tubules, and inflammation decreased. CONCLUSIONS: Amifostine prevented sepsis-related acute kidney injury by reducing inflammation and oxidative stress.

High dose zoledronic acid increases ischemia-reperfusion damage of the liver.

OBJECTIVE: Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, has been reported to exhibit a protective effect against cancers and prevent bone fractures. It also induces apoptosis by increasing proinflammatory cytokines and oxidative stress. Oxidative stress increases significantly during ischemia-reperfusion (IR) injury. The liver is highly sensitive to IR injury. In this study, we aim to investigate whether high-dose ZA treatment affects the liver during IR. MATERIALS AND METHODS: We used twenty-one Sprague-Dawley male rats in our study, and they were subdivided randomly into three groups, each containing seven rats. A single dose of 100 µg/kg ZA was administered via the intraperitoneal route in the ZA group. Forty-eight hours after the ZA administration, infrarenal abdominal aortic cross ligation was performed on the ZA and IR groups. After 2 hours of ischemia, 2 hours of reperfusion was applied. RESULTS: The malondialdehyde (MDA) level of the control group was significantly lower than the IR (p = 0.006) and ZA (p<0.001) groups. However, the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) values of the control group were significantly higher than the values of the IR group (p<0.05, p<0.001, and p<0.05) and ZA group (p = 0.002, p<0.001, and p<0.001). Caspase-3 activity was significantly higher in the IR group as compared to the control group (p<0.001). The caspase-3 activity in the ZA group, on the other hand, was higher than both the control (p<0.001) and IR groups (p<0.001). CONCLUSIONS: High-dose ZA may exacerbate liver injury during IR by increasing reactive oxygen species production and apoptosis.

Resveratrol prevents acute renal injury in a model of ruptured abdominal aortic aneurysm.

OBJECTIVE: To examine the biochemical and histopathological effects of ischemia/reperfusion (I/R) injury in a ruptured abdominal aortic aneurysm (RAAA) model in rats, and to investigate the potential protective role of resveratrol. METHODS: Thirty-two male Sprague-Dawley rats were randomly assigned into four groups-control, I/R, sham (I/R + solvent/dimethyl sulfoxide), and I/R + resveratrol. The control group underwent midline laparotomy only. In the other groups, infrarenal vascular clamps were attached following 60-min shock to the abdominal aorta. Ischemia was applied for 60 min followed by reperfusion for 120 min. In the I/R + resveratrol group, intraperitoneal 10 mg/kg resveratrol was administered 15 min prior to ischemia and immediately before reperfusion. The I/R + dimethyl sulfoxide group received dimethyl sulfoxide, and the I/R group was given saline solution. All animals were sacrificed by exsanguination from the carotid artery at the end of the experiment. In addition to histopathological examination of the rat kidney tissues, malondialdehyde, glutathione, catalase, and nitric oxide levels were also investigated. RESULTS: A decrease in glutathione, catalase and nitric oxide levels, together with increases in malondialdehyde levels, numbers of apoptotic renal tubular cells, caspase-3 levels, and tubular necrosis scores, were observed in the IR and I/R + dimethyl sulfoxide groups. In contrast, resveratrol increased glutathione, catalase and nitric oxide levels in renal tissues exposed to I/R, while reducing malondialdehyde levels, apoptotic renal tubular cell numbers, caspase-3 levels, and tubular necrosis scores. CONCLUSION: Our findings suggest that resveratrol can be effective against I/R-related acute kidney damage developing during RAAA surgery by reducing oxidative stress and apoptosis.

The effect of imatinib administered in the prenatal period on testis development in rats.

BACKGROUND: The purpose of this study was to examine the effects of exposure to imatinib in the prenatal period on testis development in rats. METHODS: Although all the study groups received intraperitoneal imatinib on prenatal days 1-8, no pregnancy occurred in the Imatinib-80 group. Immunohistochemical analysis, TUNEL, c-kit and PDGF staining revealed no difference between the groups in terms of positivity scoring. RESULTS: A significant decrease was detected in total sperm counts in the Imatinib-20 group compared to the control group, but the sperm count was higher in the Imatinib-60 group than in the Imatinib-20 group. At biochemical measurements, the drug increased oxidative stress in the testis and serum in the Imatinib-20 group, but caused a decrease in tissue in the Imatinib-60 group. Thiol measurements revealed a decrease in the testis and serum in the Imatinib-60 group, while an increase in serum measurements was observed in the Imatinib-40 group. Analysis revealed no difference between the groups in terms of protamine and histone gene expression levels in testis tissue exposed to imatinib. CONCLUSION: Our findings show that prenatal exposure to imatinib can lead to histopathological and biochemical changes in testis tissue, but that no adverse effect occurs in nuclear maturation of germ cells during spermiogenesis.

Effects of infliximab against carbon tetrachloride-induced intestinal injury via lipid peroxidation and apoptosis.

Carbon tetrachloride (CCL4) is often employed in the production of chlorofluorocarbons, petroleum refining, oil and rubber processing, and laboratory applications. Oral, subcutaneous, and inhalation exposure to CCL4 in animal studies have been shown to be capable of leading to various types of cancer (benign and malignant, liver, breast, and adrenal gland tumors). The present study also evaluated the protective role of infliximab (INF) against the deleterious effects of CCL4 on the intestinal system. Twenty-four male Sprague-Dawley rats were randomly assigned into three groups, control (n = 8), CCL4 (n = 8), and CCL4 + INF (n = 8). The control group received 1 mL isotonic saline solution only via intraperitoneal (i.p.) injection. The CCL4 group received a single i.p. dose of 2 mL/kg CCL4. The CCL4 + INF group received a single i.p. dose of 7 mg/kg INF followed 24 h later by a single dose of 2 mL/kg CCL4. All rats were euthanized 2 days following drug administration. CCL4 group samples also exhibited diffuse loss of enterocytes, vascular congestion, neutrophil infiltration, an extension of the subepithelial space and significant epithelial lifting along the length of the villi with a few denuded villous tips. In addition, CCL4 treatment increased intestinal malondialdehyde (MDA) level and caspase-3 positivity. On the other hand, INF decreased MDA levels, caspase-3 positivity, and loss of villous. Our findings suggest that CCL4 appears to exert a highly deleterious effect on the intestinal mucosa. On the other hand, INF is effective in preventing this CCL4-induced intestinal injury by reducing oxidative stress and apoptosis.

The effect of gadolinium-based contrast agents on rat testis.

Previous studies have reported that repeated administrations of linear gadolinium-based contrast agents lead to their accumulation in the brain and other tissues in individuals with normal renal functions. The purpose of this prospective animal study was to investigate the effect of multiple administrations of macrocyclic ionic (gadoteric acid) and linear nonionic (gadodiamide) gadolinium-based contrast agents (GBCAs) on rat testis tissue and to compare these molecules in terms of tissue damage. Thirty-two male Sprague-Dawley rats were kept without drugs for 5 weeks after administration of 0.1 mmol mg-1 kg-1 (0.2 ml/kg) gadodiamide and gadoteric acid for 4 days over 5 weeks. Biochemical, histopathological and immunohistochemical changes in testis tissue were evaluated at the end of 10 weeks. When used in repeated clinical doses, gadolinium was observed to increase apoptosis in the Leydig cells of the rat testis, and to increase serum Ca+2 levels and reduce testosterone levels (p < .05). Although the difference was not statistically significant, a greater loss of spermatozoa and immature germinal cell accumulation were observed in the seminiferous tubule lumen in the GBCA groups compared with the control and saline groups (p > .05). Both linear and macrocyclic contrast agents have toxic effects on testis tissue, irrespective of the type of drug.

Lasting hepatotoxic effects of prenatal mobile phone exposure.

OBJECTIVE: In this study, the livers of rats born to mothers exposed to electromagnetic field (EMF) were examined 60 days postpartum for biochemical and histopathological changes. METHODS: Pregnant rats were exposed to radiation (900 MHz EMF, 24 h/day for 20 days) using a digital signal generator by placing the device centrally under the cage, which formed the study (EMF) group, while untreated matching rats served as controls. Livers and blood were obtained from litters (seven males and seven females) of both groups 60 days after birth, which were used for biochemical and histopathological analyses. RESULTS: There was a significant increase in the levels of malondialdehyde (MDA) (p < 0.05) that was accompanied by a significant fall in glutathione (GSH) (p < 0.01) in the liver. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly increased (p < 0.05). Histopathologically, the liver sections of the EMF group showed intense degeneration in hepatocytes with cytoplasmic eosinophilic structures, pyknotic nuclei and fibrosis. CONCLUSION: We demonstrate that the intrauterin harmful effects of EMF on the livers of rats persist into adulthood.

Topiramate has protective effect on renal injury.

BACKGROUND: Topiramate (TPM) decreases tumor necrosis factor-alpha (TNF-α) and oxidative stress. We investigated protective effects of TPM on cell damage in kidney tissue during ischemia-reperfusion (I/R) damage. METHODS: A total of 30 male Wistar albino rats were divided into three groups: control, I/R, and I/R plus TPM (I/R+TPM). Laparotomy without I/R injury was performed in control group. After laparotomy, cross ligation of infrarenal abdominal aorta was applied for two hours in I/R groups which was followed by two hours of reperfusion. TPM (100 mg/kg/day) was orally administrated to animals in the I/R+TPM group for seven consecutive days before I/R. RESULTS: The I/R group's TNF-α and interleukin-1 beta (IL-1ß) levels were significantly higher (1184.2 ± 129.1 pg/mg protein; 413.1 ± 28.8 pg/mg protein, respectively) than those of the control (907.8 ± 113.0 pg/mg protein, p = 0.002; 374.7 ± 23.7 pg/mg protein, p = 0.010, respectively) and I/R+TPM groups (999.5 ± 115.2 pg/mg protein, p < 0.001; 377.9 ± 30.9 pg/mg protein, p = 0.007, respectively). CONCLUSION: TPM may partially prevent renal damage in rats. The opening of new horizons of this kind of knowledge will help understand the complex challenge in the prevention of renal I/R damage (Tab. 1, Fig. 3, Ref. 42).

Hepatic effects of ketamine administration for 2 weeks in rats.

The aim of the present study was to investigate the long-term and high-dose application of ketamine on the liver by employing histologic and biochemical methods. A total of 30 male rats were randomly assigned to control and four treatment groups (n: 6). Saline for control group and different doses of ketamine for four treatment groups (40, 60, 80 and 100 mg kg⁻¹) were administered intraperitoneal twice a day for 2 weeks. Immunohistological staining, light and electron microscopy were used to study tissue specimens. Histopathological changes were more severe and diverse in groups 80 and 100 mg kg⁻¹ day⁻¹, and the least significant change was observed in groups 40 and 60 mg kg⁻¹ day⁻¹. The most important ultrastructural changes were seen in mitochondria and in the rough endoplasmic reticulum. The immunoreactivity of calcineurin was determined as different. Prolonged use of ketamine caused hepatocellualar toxicity and histological changes in hepatocytes in a dose-dependent manner in all experimental groups.

Effects of sugammadex and rocuronium mast cell number and degranulation in rat liver.

We investigated the effect of rocuronium- and sugammadex-induced mast cell increase and degranulation in rat portal triads. Forty-two rats, in six groups, received either rocuronium 1 mg.kg(-1); sugammadex 15 mg.kg(-1); sugammadex 100 mg.kg(-1); rocuronium 1 mg.kg(-1) and 5 min later, sugammadex 15 mg.kg(-1); rocuronium 1 mg.kg(-1) and 5 min later, sugammadex 100 mg.kg(-1); or isotonic saline. Total mast cell numbers were significantly higher with rocuronium only, than in all other groups (p<0.003), although in all active groups, the number was greater than the control. Total mast cell number was significantly higher with rocuronium and low-dose sugammadex compared with low-dose sugammadex only. The number of tryptase-positive mast cells with rocuronium only was significantly higher than in all other groups (p<0.003). Tryptase-positive mast cell numbers in both groups receiving both rocuronium and sugammadex were significantly higher compared with both groups receiving sugammadex only. Rocuronium increased mast cell numbers, and degranulation was mitigated by sugammadex. These results suggest that sugammadex may be beneficial in treatment of rocuronium-induced anaphylaxis.

Protective effects of hyperbaric oxygen and iloprost on ischemia/reperfusion-induced lung injury in a rabbit model.

BACKGROUND: The role of multiorgan damage in the mortality caused by ischemic limb injury is still not clarified. The objective of this study was to examine the potential protective effects of hyperbaric oxygen (HBO) and iloprost (IL) therapy on lung damage induced by limb ischemia/reperfusion injury in a rabbit model, using both biochemical and histopathological aspects. METHODS: Forty New Zealand white rabbits were randomly allocated into one of five study groups: HBO group (single session of HBO treatment); IL group (25 ng/kg/min infusion of IL); HBO + IL group (both HBO and IL); Control group (0.9% saline only); and a sham group. Acute hind limb ischemia-reperfusion was established by clamping the abdominal aorta for 1 h. HBO treatment and IL infusion were administrated during 60 min of ischemia and 60 min of reperfusion period. Blood pH, partial pressure of oxygen, partial pressure of carbon dioxide and levels of bicarbonate, sodium, potassium, creatine kinase, lactate dehydrogenase, and tumor necrosis factor alpha were determined at the end of the reperfusion period. Malondialdehyde was measured in the plasma and lung as an indicator of free radicals. After sacrifice, left lungs were removed and histopathological examination determined the degree of lung injury. RESULTS: In the control group, blood partial pressure of oxygen and bicarbonate levels were significantly lower and creatine kinase, lactate dehydrogenase, malondialdehyde and tumor necrosis factor-α levels were significantly higher than those of the HBO group, IL group, HBO + IL group and sham group. Similarly, the malondialdehyde levels in the lung tissue and plasma levels were significantly lower in the treatment groups compared with the control group. The extent of lung injury according to the histological findings was significantly higher in the control group. CONCLUSIONS: These results suggest that both HBO and IL therapies and their combination might be effectively used in the prevention of lung injury after ischemia/reperfusion injury of the lower extremities.