Schisandra chinensis Oil Attenuates Aristolochic Acid I-Induced Nephrotoxicity in vivo and in vitro / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effects of Schisandra chinensis oil (SCEO) against aristolochic acid I (AA I)-induced nephrotoxicity in vivo and in vitro and elucidate the underlying mechanism.@*METHODS@#C57BL/6 mice were randomly divided into 5 groups according to a random number table, including control group, AA I group, and AA I +SCEO (0.25, 0.5 and 1 g/kg) groups (n=5 per group). Pretreatment with SCEO was done for 2 days by oral administration, while the control and AA I groups were treated with sodium carboxymethyl cellulose. Mice of all groups except for the control group were injected intraperitoneally with AA I (5 mg/kg) from day 3 until day 7. Histopathological examination and apoptosis of kidney tissue were observed by hematoxylin and eosin and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatinine (SCr), as well as renal malondialdehyde (MDA), glutathione, r-glutamyl cysteingl+glycine (GSH), and superoxide dismutase (SOD) were analyzed using enzyme-linked immunosorbent assay (ELISA). Expressions of hepatic cytochrome P450 1A1 (CYP1A1), CYP1A2, and nad(p)hquinonedehydrogenase1 (NQO1) were analyzed using ELISA, quantitative real-time polymerase chain reaction (qPCR) and Western blot, respectively. In vitro, SCEO (40 µ g/mL) was added 12 h before treatment with AA I (40 µ mol/mL for 48 h) in human renal proximal tubule cell line (HK-2), then apoptosis and reactive oxygen species (ROS) were analyzed by flow cytometry.@*RESULTS@#SCEO 0.5 and 1 g/kg ameliorated histopathological changes and TUNEL+ staining in the kidney tissues of mice with AA I-induced nephrotoxicity, and reduced serum levels of ALT, AST, BUN and SCr (P<0.01 or P<0.05). SCEO 0.5 and 1 g/kg alleviated the ROS generation in kidney, containing MDA, GSH and SOD (P<0.01 or P<0.05). SCEO 1 g/kg increased the expressions of CYP1A1 and CYP1A2 and decreased NQO1 level in the liver tissues (P<0.01 or P<0.05). Besides, in vitro studies also demonstrated that SCEO 40 µ g/mL inhibited apoptosis and ROS generation (P<0.05 or P<0.01).@*CONCLUSIONS@#SCEO can alleviate AA I-induced kidney damage both in vivo and in vitro. The protective mechanism may be closely related to the regulation of metabolic enzymes, thereby inhibiting apoptosis and ROS production.

Alleviation of diabetes-induced hepatotoxicity by date palm hydroalcoholic extract in rat model; a biochemical, immunohistochemical and stereological study / Alivio de la hepatotoxicidad inducida por diabetes mediante el extracto hidroalcohólico de palmera datilera en modelo de rata: un estudio bioquímico, inmunohistoquímico y estereológico

SUMMARY: The present study was aimed to investigate the hepatoprotective effects of date palm hydroalcoholic extract (DP)in diabetic rats using biochemical and histopathological approaches. Diabetes was induced by administration of 60 mg/kg of streptozotocin intraperitoneally. In this analysis 32 adult rats were randomly divided into four groups; group 1: non-diabetic control whic received 0.1 mL normal saline, group 2:served as non-diabetic control which treated with 270 mg/kg of DP, group 3: served as untreated diabetic, and group 4: diabetic rats treated with 270 mg/kg of DP. Diabetic rats treated with the DP extracts exhibited lower hepatic oxidative stress and lower hepatic enzymes level. Extract treatment decreased the level of malondealdehyde (MDA) as a marker of lipid peroxidation. Stereological estimations revealed a significant increase in the liver volume in diabetic rats which was reduced in DP-treated rats. Immunofluorescence staining showed high synthesis of acrolein as a byproduct of lipid proxidation. While, optical density measurement revealed significant decrease in acrolein after DP administration. Histopathological examination showed severe changes in untreated diabetic liver tissue manifested by dilated portal vein, leukocytic infiltration, fatty degeneration and necrotic nuclei, whereas, DP treatment attenuated the adverse effects of diabetes on the liver represented by relatively healthy hepatocytes and sinusoids. The obtained results indicated that date pam extract was beneficial in the prevention of diabetes-induced hepatotoxicity due to its natural antioxidant constituents. Further preclinical and clinical studies are needed for considering this plant in management of prediabetes and diabetes hepatic complications.

RESUMEN: El presente estudio tuvo como objetivo investigar los efectos hepatoprotectores del extracto hidroalcohólico (DP) de la palmera datilera en ratas diabéticas utilizando enfoques bioquímicos e histopatológicos. La diabetes fue inducida mediante la administración de 60 mg / kg de estreptozotocina por vía intraperitoneal. Se dividieron al azar 32 ratas adultas en cuatro grupos; grupo 1: control no diabético que recibió 0,1 mL de solución salina normal, grupo 2: control no diabético tratado con 270 mg / kg de DP, grupo 3: fue separado como diabético no tratado, y grupo 4: ratas diabéticas tratadas con 270 mg / kg de DP mg / kg de DP. Las ratas diabéticas tratadas con los extractos de DP mostraron menor estrés oxidativo hepático y menor nivel de enzimas hepáticas. El tratamiento con extracto disminuyó el nivel de malondealdehído (MDA) como marcador de la proxidación de lípidos. Las estimaciones estereológicas revelaron un aumento significativo en el volumen del hígado en ratas diabéticas que se redujo en las ratas tratadas con DP. La tinción por inmunofluorescencia mostró una alta síntesis de acroleína como subproducto de la proxidación de lípidos. Mientras que, la medición de la densidad óptica reveló una disminución significativa de la acroleína después de la administración de DP. El examen histopatológico mostró cambios significativos en el tejido hepático diabético no tratado manifestados por vena porta dilatada, infiltración leucocítica, degeneración grasa y núcleos necróticos, mientras que el tratamiento con DP atenuó los efectos adversos de la diabetes en el hígado representados por hepatocitos y sinusoides relativamente sanos. Los resultados obtenidos indicaron que el extracto de palmera datilera fue beneficioso en la prevención de la hepatotoxicidad inducida por diabetes debido a sus constituyentes antioxidantes naturales. Se necesitan más estudios clínicos para considerar esta planta en el manejo de la prediabetes y las complicaciones hepáticas de la diabetes.

lncRNA PCGEM1 strengthens anti-inflammatory and lung protective effects of montelukast sodium in children with cough-variant asthma

Montelukast sodium is an effective and well-tolerated anti-asthmatic drug. Long non-coding RNAs (lncRNAs) are involved in the treatment of asthma. Therefore, this study aimed to investigate the effect of montelukast sodium on children with cough-variant asthma (CVA) and the role of lncRNA prostate cancer gene expression marker 1 (PCGEM1) in drug efficacy. The efficacy of montelukast sodium was evaluated by assessing the release of inflammatory factors and pulmonary function in CVA children after a 3-month treatment. An ovalbumin (OVA)-sensitized mouse model was developed to simulate asthmatic conditions. PCGEM1 expression in clinical peripheral blood samples and lung tissues of asthmatic mice was determined. Asthmatic mice experienced nasal inhalation of PCGEM1 overexpression with simultaneous montelukast sodium to investigate the roles of PCGEM1 in asthma treatment. The NF-κB axis after PCGEM1 overexpression was detected to explore the underling mechanisms. Consequently, montelukast sodium contributed to reduced levels of pro-inflammatory factors and improved pulmonary function in CVA children. PCGEM1 was poorly expressed in OVA-sensitized asthmatic mice and highly expressed in CVA children with response to the treatment. PCGEM1 overexpression enhanced the anti-inflammatory effects and promoted effects on pulmonary function of montelukast sodium in CVA children and OVA-sensitized asthmatic mice. Furthermore, PCGEM1 inhibited the activation of the NF-κB axis. This study demonstrated the anti-inflammatory and lung-protective effects of montelukast sodium on CVA, which was strengthened by overexpression of PCGEM1. Findings in this study highlighted a potential anti-asthmatic target of montelukast sodium.

Investigation of Protective Effect of Matricaria Chamomilla L. Extract on Methotrexate-Induced Hepatotoxicity in Wistar Rat

Abstract Methotrexate (MTX) was shown to cause oxidative stress and liver damage. The objective was to investigate the possible protective effects of Matricaria Chamomilla L. (chamomile) extract with anti-oxidant and anti-inflammatory properties on the methotrexate-induced liver toxicity. Twenty four Wistar rats were divided into four groups. MTX group was injected intraperitoneally on days 7 and 14 with 20 mg/kg methotrexate. Groups CE200 (chamomile extract 200 mg/kg/day) and CE300 (chamomile extract 300 mg/kg/day) received the same dose of methotrexate added with chamomile extract orally for 15 days at 200 mg/kg and 300 mg/kg respectively and the last group was healthy control group. Results of biochemical analyses indicated serum liver biomarkers (aminotransferases), alkaline phosphatase (ALP), albumin, and liver content of anti-oxidant enzymes (catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)), reduced glutathione (GSH) and total anti-oxidant capacity (TAC) significantly increased (P <0.05-0.001) to normal in the CE treated groups compared to those of the MTX group. Serum bilirubin and hepatic malondialdehyde (MDA) levels significantly increased (P ˂0.001) in MTX group compared to those of the control group and decreased in CE200 and CE300 groups compared to those of the MTX group. Histopathological study showed inflammatory damage, necrotic cells and lipid infiltration in MTX group. In the groups treated with the chamomile extract, a significant improvement was observed in liver tissue in response to increased dose of the extract. In conclusion, chamomile extract administration could have a protective role in methotrexate-induced liver toxicity in rats through improving anti-oxidant defense system.

The Protective Effect of Lercanidipine on Indomethacin-Induced Gastric Ulcers in Rats

Abstract Nonsteroidal anti-inflammatory drugs (NSAID) are among the aggressive factors causing gastric ulcer. They cause oxidative damage in the gastric tissue and lead to intracellular calcium deposition. Lercanidipine is a calcium channel blocker derived from the third generation dihydropyridine. The aim of this study is to analyse the effect of lercanidipine on indomethacin-induced gastric ulcers. A total of 24 albino Wistar male rats were divided into four groups; those who received indomethacin 25 mg/kg (IND), 5 mg mg/kg lercanidipine +25 mg/kg indomethacin (LC-5), 10 mg/kg lercanidipine+25mg/kg indomethacin (LC-10) and healthy rats who received 0.5 mL distilled water. Six hours after the application of indomethacin, the animals were sacrificed by high dose thiopental sodium. The stomachs of the animals were excised to perform a macroscopic analysis and the ulcerous region was measured on millimeter paper. All the stomachs were subjected to a biochemical analysis. Macroscopic analysis revealed hyperaemia on the gastric surface of the indomethacin group. Ulcerous tissues formed by oval, circular or irregular mucosal defects in varying diameters and depths were observed on the whole surface of the stomach. Hyperaemia was lower and ulcerous region was smaller in groups LC-5 and LC-10 compared to IND group. Malondialdehyde and myeloperoxidase levels were significantly lower and total glutathione and cyclooxygenase-1 activity were higher in groups LC-5 and LC-10. Lercanidipine did not change the cyclooxygenase-2 activity. Lercanidipine in doses 10 mg/kg is more effective compared to 5 mg/kg. Lercanidipinine can be useful in the treatment of NSAID-induced gastric damage.

Macrophage migration inhibitory factor antagonist (p425) ameliorates kidney histopathological and functional changes in diabetic rats / Antagonista (p425) do fator de inibição da migração de macrófagos (MIF) melhora as alterações histopatológicas e funcionais renais em ratos diabéticos

Abstract Introduction: It is hypothesized that increased macrophage migration inhibitory factor (MIF) expression may contribute to diabetic nephropathy (DN) pathogenesis. The aim of the present study was to investigate the renal effects of MIF inhibition in a diabetic experimental model. Methods: Eighteen male Wistar rats (230 ± 20 g) were divided into three groups: 1) control, 2) diabetic (STZ, 50 mg/kg, dissolved in saline, ip), 3) diabetic + MIF antagonist (p425, 1 mg/kg per day, ip, on the 21th day, for 21 consecutive days). The treatment started since we founwd a significant increase in urine albumin excretion (UAE) rate in the diabetic rats in comparison with the control rats. The rats were kept individually in metabolic cages (8 AM-2 PM) and urine samples were collected in the 21 and 42th day. At the end, blood and tissue samples were collected for biochemical (BS, UPE, urine GAG, BUN, Cr, Na, and K) and histological analyses. Results: The results of this study showed that MIF antagonist (p425) significantly decreased urine protein and GAG excretion, urine protein/creatinine ratio, and serum BUN and Cr in the streptozotocin-induced DN in the rats. Pathological changes were significantly alleviated in the MIF antagonist (p425)-administered DN rats. Conclusion: Collectively, these data suggested that MIF antagonist (p425) was able to protect against functional and histopathological injury in the DN.

Resumo Introdução: Supõe-se que elevações da expressão do fator de inibição da migração de macrófagos (MIF) possam contribuir para a patogênese da nefropatia diabética (ND). O objetivo do presente estudo foi investigar os efeitos renais da inibição do MIF em um modelo experimental diabético. Métodos: Dezoito ratos Wistar machos (230 ± 20g) foram divididos em três grupos: 1) controle, 2) diabético (STZ 50 mg/kg dissolvida em soro fisiológico, IP), 3) diabético + antagonista do MIF (p425 1 mg/kg por dia IP no 21o dia por 21 dias consecutivos). O tratamento começou após a identificação de aumento significativo na albuminúria nos ratos diabéticos em relação aos controles. Os ratos foram mantidos individualmente em gaiolas metabólicas (8h-14h) e amostras de urina foram colhidas no 21o e no 42o dia. Ao final do estudo, amostras de sangue e tecido foram colhidas para análises bioquímicas (BS, excreção urinária de proteína, excreção urinária de GAGs, BUN, Cr, Na e K) e histológicas. Resultados: O presente estudo demonstrou que o antagonista do MIF (p425) diminuiu significativamente proteinúria, excreção urinária de GAGs , relação proteína/creatinina na urina, BUN e Cr no grupo com ND induzida por estreptozotocina. As alterações patológicas foram significativamente abrandadas nos ratos com ND que receberam antagonista do MIF (p425). Conclusão: Coletivamente, os dados sugerem que o antagonista do MIF (p425) teve efeito protetor contra lesões funcionais e histopatológicas da ND.

Comparative analysis of myocardial protection with htk solution and hypothermic hyperkalemic blood solution in the correction of acyanogenic congenital cardiopathies - a randomized study

Abstract Objective: The goal of the present study was to compare the myocardial protection obtained with histidine-tryptophan-ketoglutarate (HTK) cardioplegic solution (Custodiol®) and with intermittent hypothermic blood solution. Methods: Two homogenous groups of 25 children with acyanotic congenital heart disease who underwent total correction with mean aortic clamping time of 60 minutes were evaluated in this randomized study. Troponin and creatine kinase-MB curves, vasoactive-inotropic score, and left ventricular function were obtained by echocardiogram in each group. The values were correlated and presented through graphs and tables after adequate statistical treatment. Results: It was observed that values of all the studied variables varied over time, but there was no difference between the groups. Conclusion: We conclude that in patients with acyanotic congenital cardiopathies submitted to total surgical correction, mean aortic clamping time around one hour, and cardiopulmonary bypass with moderate hypothermia, the HTK crystalloid cardioplegic solution offers the same myocardial protection as the cold-blood hyperkalemic cardioplegic solution analyzed, according to the variables considered in our study model.

The protective effects of whortleberry extract against cisplatin-induced ototoxicity in rats / Efeitos protetores do extrato de uva-do-monte contra a ototoxicidade induzida por cisplatina em ratos

Abstract Introduction: Cisplatin is one of the main chemotherapeutic agents used for the treatment of many types of cancer. However, ototoxicity, one of the most serious side effects of cisplatin, restricts its usage. Objective: We aimed to investigate the protective effects of whortleberry extract against cisplatin-induced ototoxicity by evaluating hearing and histopathological cochlear damage and by measuring the biochemical parameters affected byoxidative stress. Methods: Forty-eight male rats were included in the study after performing Distortion Product Otoacoustic Emission test to confirm that their hearing levels were normal. The rats were randomly divided into six groups: the control group, the sham group, and, which received only whortleberry extract, only cisplatin, cisplatin + 100 mg whortleberry extract, cisplatin + 200 mg whortleberry extract, respectively. Audiologic investigation was performed by performing the Distortion Product Otoacoustic Emission test at the beginning and at the eighth day of the study. Cardiac blood samples were collected for biochemical analysis, and the rats were sacrificed to obtain cochlear histopathological specimens on the eighth day. Results: The results revealed that whortleberry protects hearing against cisplatin-induced ototoxicity independent of the dose. However, high doses of whortleberry extract are needed to prevent histopathological degeneration and oxidative stress. Conclusion: The results obtained in this study show that whortleberry extract has a protective effect against cisplatin-induced ototoxicity.

Resumo Introdução: A cisplatina é um dos principais agentes quimioterápicos utilizados para o tratamento de muitos tipos de câncer. No entanto, a ototoxicidade, um dos efeitos colaterais mais graves da cisplatina, restringe seu uso. Objetivo: Nosso objetivo foi investigar os efeitos protetores do extrato de uva-do-monte contra a ototoxicidade induzida por cisplatina, avaliar o dano auditivo e histopatológico coclear e medir os parâmetros bioquímicos afetados pelo estresse oxidativo. Método: Foram incluídos no estudo 48 ratos machos após teste de emissão otoacústica evocada por produto de distorção para confirmar que seus níveis de audição eram normais. Os ratos foram divididos aleatoriamente em seis grupos: o grupo controle, o grupo simulado, o que recebeu apenas extrato de uva-do-monte, o que recebeu apenas cisplatina, o que recebeu cisplatina + 100 mg de extrato de uva-do-monte e o que recebeu cisplatina + 200 mg de extrato de uva-do-monte, respectivamente. A investigação audiológica foi feita através do teste de emissão otoacústica de produto de distorção no início e no oitavo dia do estudo. As amostras de sangue cardíaco foram coletadas para análise bioquímica e os ratos foram sacrificados para obtenção de espécimes histopatológicos cocleares no oitavo dia. Resultados: Os resultados revelaram que o extrato de uva-do-monte protege a audição contra a ototoxicidade induzida por cisplatina, independentemente da dose. No entanto, são necessárias doses elevadas do extrato para evitar a degeneração histopatológica e o estresse oxidativo. Conclusão: Os resultados obtidos neste estudo mostram que o extrato de uva-do-monte tem um efeito protetor contra a ototoxicidade induzida por cisplatina.

Milk fat globule-epidermal growth factor 8 (MFG-E8) attenuates sepsis-induced acute kidney injury by inhibiting NF-κB signaling pathway1

Abstract Purpose: To explore the effect of milk fat globule-epidermal growth factor 8 (MFG-E8) on sepsis-induced acute kidney injury (SAKI). Methods: Male C57BL/6 mice were randomized to control, sham, CLP, CLP+PBS, and CLP+rmMFG-E8 groups. SAKI was induced by cecal ligation and puncture (CLP). Recombinant mouse MFG-E8 (rmMFG-E8) (20 μg/kg) or PBS (vehicle) was administered intraperitoneally. Blood, urine and renal tissue were collected at 24 h after CLP. Blood samples were tested for serum kidney injury biomarker and cytokines. Urine samples were collected to detect KIM-1, and NGAL. Real-time PCR was tested for Bax and Bcl-2. TUNEL staining was used to determine renal apoptosis. Western blot was used to detect the expression of Bax, Bcl-2, and proteins in the NF-κB pathway. Results: MFG-E8 alleviated SAKI by decreasing serum Cre, BUN, urine KIM-1 and NGAL and by mitigating renal pathological changes significant (p < 0.05). IL-1β, IL-6, TNF-α were significantly inhibited by MFG-E8 (p < 0.05). Apoptosis induced by SAKI was markedly suppressed by MFG-E8. Finally, MFG-E8 attenuated the activation of the NF-��B signaling pathway in SAKI. Conclusion: MFG-E8 has beneficial effects on SAKI, which may be achieved by inhibiting the NF-κB pathway.

Protective effect of dexmedetomidine against organ dysfunction in a two-hit model of hemorrhage/resuscitation and endotoxemia in rats

Dexmedetomidine (DEX), a selective agonist of α2-adrenergic receptors, has anti-inflammation properties and potential beneficial effects against trauma, shock, or infection. Therefore, this study aimed to investigate whether DEX might protect against multiple-organ dysfunction in a two-hit model of hemorrhage/resuscitation (HS) and subsequent endotoxemia. Eighty Wistar rats were randomized into four groups: NS (normal saline), HS/L (HS plus lipopolysaccharide), HS/L+D (HS/L plus dexmedetomidine), and HS/L+D+Y (HS/L+D plus yohimbine). Six hours after resuscitation, blood gas (PaO2) and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urine nitrogen (BUN), creatinine (Cr), TNF-α, IL-β, IL-6, IL-8, IL-10, and nitric oxide (NO) were measured. The histopathology was assayed by staining. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels and heme oxygenase-1 (HO-1) were assayed. The PaO2 levels in HS/L rats were lower whereas the ALT, AST, BUN, Cr, TNF-α, IL-β, IL-6, IL-8, IL-10, and NO levels were higher compared to the control group. The HS/L+D increased PaO2 and further increased IL-10 and decreased ALT, AST, BUN, Cr, TNF-α, IL-β, IL-6, IL-8, and NO levels of the HS/L groups. In addition, the MDA in the HS/L groups increased whereas SOD activity decreased compared to the control group. Moreover, the HO-1 expression levels were increased by DEX administration in lung, liver, and kidney tissues. Lungs, livers, and kidneys of the HS/L group displayed significant damage, but such damage was attenuated in the HS/L+D group. All of the above-mentioned effects of DEX were partly reversed by yohimbine. DEX reduced multiple organ injury caused by HS/L in rats, which may be mediated, at least in part, by α2-adrenergic receptors.

Amifostine reduces inflammation and protects against 5-fluorouracil-induced oral mucositis and hyposalivation

Oral mucositis (OM) is a common and dose-limiting side effect of cancer treatment, including 5-fluorouracil (5-FU) and radiotherapy. The efficacy of the therapeutic measures to prevent OM is limited and disease prevention is not fully observable. Amifostine is a cytoprotective agent with a described anti-inflammatory potential. It is clinically used to reduce radiotherapy and chemotherapy-associated xerostomia. This study investigated the protective effect of amifostine on an experimental model of OM. Hamsters were divided into six groups: saline control group (5 mL/kg), mechanical trauma (scratches) of the right cheek pouch; 5-FU (60 and 40 mg/kg, ip, respectively, administered on days 1 and 2); amifostine (12.5, 25, or 50 mg/kg) + 5-FU + scratches. Salivation rate was assessed and the animals were euthanized on day 10 for the analysis of macroscopic and microscopic injury by scores. Tissue samples were harvested for the measurement of neutrophil infiltration and detection of inflammatory markers by ELISA and immunohistochemistry. 5-FU induced pronounced hyposalivation, which was prevented by amifostine (P<0.05). In addition, 5-FU injection caused pronounced tissue injury accompanied by increased neutrophil accumulation, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) tissue levels, and positive immunostaining for TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS). Interestingly, amifostine prevented the inflammatory reaction and consequently improved macroscopic and microscopic damage (P<0.05 vs 5-FU group). Amifostine reduced inflammation and protected against 5-FU-associated oral mucositis and hyposalivation.

The protective effect of Papaverine and Alprostadil in rat testes after ischemia and reperfusion injury

ABSTRACT Objective: To investigate the effect of papaverine and alprostadil on testicular torsion-detorsion injury in rats. Materials and Methods: A total of 40 male Wistar-Albino rats were used in this study. Four hours of right testicular torsion was applied to each group, excluding sham oper- ated group. The torsion-detorsion (T/D), T/D + papaverine and T/D + alprostadil groups received saline, papaverine and alprostadil at the same time as surgical detorsion, respectively. At 14 days after the surgical detorsion, ischaemic changes and the degree of damage were evaluated with Cosentino scoring and the Johnson tubular biopsy score (JTBS). Results: JTBS was determined as 8.8±2.7 in the Sham group, 5.08±1.9 in the T/D+papaverine group, 5.29±2.3 in the T/D +alprostadil group and 2.86±1.9 in the TD group. The JTBS was determined to be statistically significantly high in both the T/D + papaverine group and the T/D + alprostadil group compared to the T/D group (p=0.01, p=0.009). In the T/D + papaverine group, 3 (43%) testes were classified as Cosentino 2, 3 (43%) as Cosentino 3 and 1 (14%) as Cosentino 4. In the T/D +alprostadil group, 5 (50 %) testes were classified as Cosentino 2, 3 (30 %) as Cosentino 3 and 2 (20%) as Cosentino 4. Conclusion: The present study indicated that spermatic cord administration of alprostadil and papaverine showed a protective effect against ischemia/reperfusion injury after right-side testes torsion and histological changes were decreased after testicular ischemia reperfusion injury.

Study of the protective effect of dexamethasone on cisplatin-induced ototoxicity in rats

Abstract Purpose: To evaluate the ability of dexamethasone to protect against cisplatin (CDDP)-induced ototoxicity. Methods: Male Wistar rats were divided into the following three groups: 1) Control (C): 6 animals received intraperitoneal (IP) saline solution, 8 ml/kg/day for four days; 2) C + CDDP: 11 animals received 8 ml/kg/day of IP saline and, 90 min after saline administration, 8 mg/kg/day of IP CDDP for four days; and 3) DEXA15 + CDDP: 11 animals received IP dexamethasone 15 mg/kg/day and, 90 min after dexamethasone administration, received 8 mg/kg/day of IP CDDP for four days. Results: It was found that dexamethasone did not protect against weight loss in CDDP-exposed animals. The mortality rate was comparable with that previously reported in the literature. The auditory threshold of animals in the DEXA15 + CDDP group was not significantly altered after exposure to CDDP. The stria vascularis of animals in the DEXA15 + CDDP group was partially preserved after CDDP exposure. Conclusions: Dexamethasone at the dose of 15 mg/kg/day partially protected against CDDP-induced ototoxicity, based on functional evaluation by brainstem evoked response audiontry (BERA) and morphological evaluation by optical microscopy. However, dexamethasone did not protect against systemic toxicity.

Tadalafil: protective action against the development of multiple organ failure syndrome

Abstract Introduction: Multiple organ failure syndrome (MOFS) is a pathology associated to unspecified and severe trauma, characterized by elevated morbidity and mortality. The complex inflammatory MOFS-related reactions generate important ischemia-reperfusion responses in the induction of this syndrome. Nitric oxide elevation, through the activation of cyclic guanosine monophosphate (cGMP), has the potential of counteracting the typical systemic vasoconstriction, and platelet-induced hypercoagulation. Tadalafil would possibly act protectively by reducing cGMP degradation with consequent diffuse vasodilatation, besides reduction of platelet-induced hypercoagulation, thus, preventing multiple organ failure syndrome development. Methods: The experimental protocol was previously approved by an institution animal research committee. Experimental MOFS was induced through the stereotaxic micro-neurosurgical bilateral anterior hypothalamic lesions model. Groups of 10 Wistar rats were divided into: a) Non-operated control; b) Operated control group; c) 2 hours after tadalafil-treated operated group; d) 4 hours after tadalafil-treated operated group; e) 8 hours after post-treated operated group. The animals were sacrificed 24 hours after the neurosurgical procedure and submitted to histopathologic examination of five organs: brain, lungs, stomach, kidneys, and liver. Results: The electrolytic hypothalamic lesions resulted in a full picture of MOFS with disseminated multiple-organs lesions, provoked primarily by diffusely spread micro-thrombi. The treatment with tadalafil 2 hours after the micro-neurosurgical lesions reduced the experimental MOFS lesions development, in a highly significant level (P<0.01) of 58.75%. The treatment with tadalafil, 4 hours after the micro-neurosurgically-induced MOFS lesions, also reduced in 49.71%, in a highly significant level (P<0.01). Finally, the treatment with tadalafil 8 hours after the neurosurgical procedure resulted in a statistically significant reduction of 30.50% (P<0.05) of the experimentally-induced MOFS gravity scores. Conclusion: The phosphodiesterase 5 inhibitor, tadalafil, in the doses and timing utilized, showed to protect against the experimentally-induced MOFS.

Dexmedetomidine protects against renal ischemia and reperfusion injury by inhibiting the P38-MAPK/TXNIP signaling activation in streptozotocin induced diabetic rats

Abstract Purpose: To determine whether dexmedetomidine (DEX) could attenuate acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) in streptozotocin (STZ)-induced diabetic rats. Methods: Four groups each containing six rats were created (sham control(S), diabetes-sham (DS), diabetes I/R (DI/R), and diabetes-I/R-dexmedetomidine (DI/R-DEX). In diabetes groups, single-dose (65 mg/kg) STZ was administered intraperitoneally (i.p.). In Group DI/R, ischemia reperfusion was produced via 25 min of bilateral renal pedicle clamping followed by 48 h of reperfusion. In Group DI/R-DEX, 50 μg/kg dexmedetomidine was administered intraperitoneally 30 minutes before ischemia. Renal function, histology, apoptosis, the levels of TNF-α, IL-1β, and oxidative stress in diabetic kidney were determined. Moreover, expression of P38 mitogen-activated protein kinase (P38-MAPK), phosphorylated-P38-MAPK(p-P38-MAPK) and thioredoxin-interacting protein (TXNIP) were assessed. Results: The degree of renal I/R injury was significantly increased in DI/R group compared with S group and DS group. The levels of TNF-α, IL-1β, oxidative stress and apoptosis were found significantly higher in DI/R Group when compared with S Group and DS Group. The protein expression of p-P38-MAPK and TXNIP were significantly increased after I/R. All these changes were reversed by DEX treatment. Conclusion: The renoprotective effects of DEX-pretreatment which attenuates I/R-induced AKI were partly through inhibition of P38-MAPK activation and expression of TXINP in diabetic kidney.

Evaluation of silybum marinaum efficacy on University of Wisconsin and histidine-tryptophan-ketoglutarate solutions latter the damage of the perfused liver

Abstract Purpose: To investigate the hepatoprotective and antioxidant effeicacies of Silybum marianum's (silymarin, S) on University of Wisconsin (UW) and histidinetryptophan-ketoglutarate (HTK) preservation solutions. Methods: Thirty two Wistar albino adult male rats were used. Group 1: UW group, Group 2: UW + Silymarin group(S), Group 3: HTK group, Group 4: HTK + silymarin group (S), respectively. Silymarin was enforced intraperitoneally before the surgery. Biopsies were enforced in 0, 6 and 12.hours to investigate. Results: Biochemical parameters examined in alanine aminotransferase (ALT), furthermore superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in rats were also evaluated. Detected histopathological changings were substantially declining in the groups that received silymarin, cellular damage was decreased significantly in HTK + Silymarin group, according to other groups. It has been identified as the most effective group was HTK + silymarin group in evaluation of ALT, electron microscopic results, also decreased MDA and elevated in SOD, and CAT activity. Caspase 3 analysis showed a substantial lower apoptosis ratio in the silymarin groups than in the non-performed groups (p<0.05). Conclusion: Histidinetryptophan-ketoglutarate+silymarin group provides better hepatoprotection than other groups, by decreasing the hepatic pathologic damage, delayed changes that arise under cold ischemic terms.

In situ effect of CPP-ACP chewing gum upon erosive enamel loss

Abstract Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is able to increase salivary calcium and phosphate levels at an acidic pH. Previous studies demonstrated that a CPP-ACP chewing gum was able to enhance the re-hardening of erosion lesions, but could not diminish enamel hardness loss. Therefore, there is no consensus regarding the effectiveness of CPP-ACP on dental erosion. Objective This in situ study investigated the ability of a CPP-ACP chewing gum in preventing erosive enamel loss. Material and Methods: During three experimental crossover phases (one phase per group) of seven days each, eight volunteers wore palatal devices with human enamel blocks. The groups were: GI - Sugar free chewing gum with CPP-ACP; GII - Conventional sugar free chewing gum; and GIII - No chewing gum (control). Erosive challenge was extraorally performed by immersion of the enamel blocks in cola drink (5 min, 4x/day). After each challenge, in groups CPP and No CPP, volunteers chewed one unit of the corresponding chewing gum for 30 minutes. Quantitative analysis of enamel loss was performed by profilometry (µm). Data were analyzed by Repeated-Measures ANOVA and Tukey's test (p<0.05). Results The use of chewing gum (CPP and No CPP) resulted in lower erosive enamel loss compared with the control group (p<0.05). CPP-ACP chewing gum (CPP) did not improve the protection against erosive enamel loss compared with conventional chewing gum (No CPP) (p>0.05). Conclusion The CPP-ACP chewing gum was not able to enhance the anti-erosive effect of conventional chewing gum against enamel loss.

Protective effects of fentanyl preconditioning on cardiomyocyte apoptosis induced by ischemia-reperfusion in rats

We aimed to study the effect of fentanyl (Fen) preconditioning on cardiomyocyte apoptosis induced by ischemia-reperfusion (I/R) in rats. A total of 120 Sprague Dawley male rats (age: 3 months) were randomly divided into: sham operation group (S group), I/R group, normal saline I/R group (NS group), and fentanyl low, middle, and high dose groups (Fen1: 2 μg/kg; Fen2: 4 μg/kg; Fen3: 6 μg/kg). Heart rate (HR), mean arterial pressure (MAP), left ventricular developed pressure (LVDP), ±dp/dtmax, malondialdehyde (MDA), superoxide dismutase (SOD) activity, creatine phosphokinase-MB (CK-MB), and cardiac troponin-I (cTnI) were measured. Myocardial ischemic (MI) area, total apoptotic myocardial cells, and protein and mRNA expressions of B-cell lymphoma 2 (Bcl-2) and Bax were detected. HR and MAP were higher, while LVDP and ±dp/dtmax were close to the base value in the Fen groups compared to those in the I/R group. Decreased MDA concentration and CK-MB value and increased SOD activity were found in the Fen groups compared to the I/R group, while cTnI concentration was significantly lower in the Fen1 and Fen2 groups (all P<0.05). Myocardial damage was less in the Fen groups compared to the I/R group and the MI areas and apoptotic indexes were significantly lower in the Fen1 and Fen2 groups (all P<0.05). Furthermore, significantly increased protein and mRNA expressions of Bcl-2, and decreased protein and mRNA expressions of Bax were found in the Fen groups compared to the I/R group (all P<0.05). Fentanyl preconditioning may suppress cardiomyocyte apoptosis induced by I/R in rats by regulating Bcl-2 and Bax.

Efecto hepatoprotector del Asparagus officinalis (Espárrago verde) en daño inducido por fármacos antituberculosos / Hepatoprotective effect of Asparagus officinalis (green asparagus) on damage induced by tuberculostatic agents

Objetivos: Evaluar el efecto hepatoprotector del extracto acuoso del Asparagus officinalis (AO) en daño inducido por fármacos antituberculosos. Materiales y métodos: Diseño experimental, se utilizó ratas Holtzman macho (n= 32) y tallos de AO. Se conformó cuatro grupos de ratas (n=8): G1: control con solución salina fisiológica (SSF) por vía oral (VO), G2, G3 y G4 con AO a dosis de 25, 50 y 100 mg/kg respectivamente; todos los grupos recibieron isoniazida (I) y rifampicina (R) a razón de 50 mg/kg durante 21 días. Se realizó punción cardiaca para evaluación seriada de enzimas hepáticas; finalmente, las ratas fueron sacrificadas para análisis histopatológico. Se evaluó la variación de peso, cambios en heces y orinas. Niveles de transaminasas (ALT y AST), bilirrubina total (BT), evaluación macroscópica de hígado y estructura hepatocelular. Se aplicó la prueba paramétrica de ANOVA y post-hoc Sheffe, y las no paramétricas de Kruskal-Wallis y Mann Whitney. El análisis se realizó con el paquete estadístico SPSS V20 y se consideró significativo un p<0,05. Resultados: El peso disminuyó 8,06% en el grupo G1. Las heces y orinas fueron de color marrón oscuro en mayor porcentaje en G1. Los niveles de ALT y AST resultaron mayores en G1 a los días 11 y 21 con respecto a G2, G3 y G4 (prueba ANOVA [p< 0,01], Scheffe (p< 0,01)). El Grupo G1 presentó severa infiltración de células inflamatorias, marcada congestión alrededor de vena centrolobulillar y severa dilatación de sinusoides a diferencia de G2, G3 y G4. Conclusiones: En condiciones experimentales el extracto acuoso del Asparagus officinalis tiene efecto hepatoprotector ante el daño inducido por fármacos antituberculosos (I + R).