Anesthesia and analgesia for common research models of adult mice / 한국실험동물학회지

Anesthesia and analgesia are major components of many interventional studies on laboratory animals. However, various studies have shown improper reporting or use of anesthetics/analgesics in research proposals and published articles. In many cases, it seems “anesthesia” and “analgesia” are used interchangeably, while they are referring to two different concepts. Not only this is an unethical practice, but also it may be one of the reasons for the proven sub‑ optimal quality of many animal researches. This is a widespread problem among investigations on various species of animals. However, it could be imagined that it may be more prevalent for the most common species of laboratory animals, such as the laboratory mice. In this review, proper anesthetic/analgesic methods for routine procedures on laboratory mice are discussed. We considered the available literature and critically reviewed their anesthetic/analge‑ sic methods. Detailed dosing and pharmacological information for the relevant drugs are provided and some of the drugs’ side effects are discussed. This paper provides the necessary data for an informed choice of anesthetic/analge‑ sic methods in some routine procedures on laboratory mice.

Role of angiotensin type 2 receptor on nitric oxide production response to angiotensin II administration in ovariectomised rats treated with estradiol

Renin-angiotensin system activity is gender related. The vasodilatory response of angiotensin II [AngII] angiotensin type 2 receptor [AT2R] may involve nitric oxide [NO] production. We attempted to find the role of AT2R on NO formation response to AngII administration in ovariectomised rats treated with estradiol [OVE]. A total of 33 female Wistar rats were divided into 3 groups; intact animals, ovariectomised treated with placebo [OVX] and OVE. At 2 weeks later, all animals were subjected to anesthetize and catheterize and each group was divided into two subgroups that received AT2R antagonist [PD123319] or vehicle. Each animal was subjected to 1 h continuous infusion of AngII [20 miceog/kg/h] and the level of NO metabolite [nitrite] was measured before and after AngII infusion. At the presence of AT2R, the serum level of nitrite in response to AngII administration in OVE groups increased significantly [P < 0.05]. However, this increase was abolished by AT2R antagonist. It seems that AT2R involves nitrite production response to AngII in OVE

N-acetylcysteine prevents kidney and lung disturbances in renal ischemia/ reperfusion injury in rat

One of the most common causes of acute kidney injury [AKI] is kidney ischemia/reperfusion injury [IRI]. The distant organ injury such as acute lung injury is one of the side effects of AKI or kidney IRI. In this study, we performed bilateral renal IRI in rats and the protective role of N acetylcysteine [NAC] in kidney and lung was investigated. Rats [n = 30] were randomly assigned to four experiment groups. The group 1 was assigned as sham operated group. Before kidney IRI performance, the others groups were treated with saline [group 2], 150 mg/kg [group 3] or 500 mg/kg [group 4] of NAC, and the treatment were continued daily after IRI for next 3 days. At day 3, the all groups' animals were subjected for the measurements. The serum level of blood urea nitrogen [BUN] and creatinine [Cr] in the control group increased significantly [P < 0.05], and administration of NAC [150 mg/kg] decreased the serum levels of Cr and BUN. However, only the serum level of Cr decreased significantly [P < 0.05]. NAC did not improve kidney weight and damage; however, its low dose [150 mg/kg] attenuated the lung injury score [P < 0.05] when compared with the control group. No significant differences were observed in lung water content and endothelial permeability, serum levels of malondialdehyde and nitrite between the groups. Low dose of NAC as a protectant agent may protect the kidney function and lung tissue damage after kidney IRI

Protective role of silymarin and deferoxamine against iron dextran-induced renal iron deposition in male rats

Kidney iron deposition [KID] is caused by iron overload that is observed in kidney diseases and anemia. The protective effects of deferoxamine [DF] and silymarin [SM] were studied against iron overload-induced KID in rat model. Rats received iron dextran [200 mg/kg] for a period of 4 weeks every other day, but at the beginning of week 3, they also were subjected to a 2-week [every other day] treatment with vehicle [group 2, positive control], SM [200 mg/kg; group 3], DF [50 mg/kg; group 4], SM [400 mg/kg; group 5], and combination of SM and DF [200 and 50 mg/kg, respectively; group 6]. Group 1, as the negative control, received saline alone during the study. The levels of serum creatinine [Cr], blood urea nitrogen [BUN], iron, ferritin, and nitrite were determined, and the kidney was removed for histopathological investigations. Before treatment, the serum levels of iron and ferritin in all iron dextran receiver groups were significantly higher than those of the negative control group [P < 0.05]. However, the serum levels of BUN, Cr, and nitrite were not different between the groups. No statistical differences were detected in kidney weight and the serum levels of BUN, Cr, iron, ferritin, and nitrite after 2 weeks of treatment with SM, DF, or combination of both. The SM and DF treatments reduced the intensity of the KID, but only in the SM [200 mg/kg] group, a significant reduction in KID was observed [P < 0.05]. It seems that SM is a nephroprotectant agent against KID in acute iron overload animal models

Angiotensin 1-7 receptor and angiotensin II receptor 2 blockades prevent the increased serum and kidney nitric oxide levels in response to angiotensin II administration: Ggender-related difference

The angiotensin II [Ang II] receptor 2 [AT2R] and angiotensin 1-7 receptor [masR] expression in the kidney are gender-related. We attempted to compare the response of nitric oxide [NO] production to Ang II administration, with and without AT2R and masR blockades, using A-779 and PD123319 in male and female rats. Anesthetized and catheterized male and female Wistar rats were subjected to one-hour continuous infusion of Ang II [tilde20 microg/kg/hour], with and without masR and AT2R blockades. The level of the NO metabolite [nitrite] was measured before and after the experiment in rat serum and in the homogenized kidney tissue. The basal data indicated that no sex difference in the serum level of nitrite could be detected before Ang II infusion. However, administration of Ang II in male and female rats caused a gender difference in the nitrite level, which resulted in the serum level of the nitrite significantly increasing in males [P < 0.05] when compared with the females. In addition, masR blockade or co-blockade of masR and AT2R in male rats abolished the gender difference related to the effect of Ang II on nitrite production. In the presence of masR and AT2R, or when masR alone was blocked, the level of nitrite in the kidney, in response to the Ang II infusion was not significantly different between the two sexes. On the contrary, masR and AT2R co-blockades significantly decreased the kidney nitrite concentration response to Ang II administration in both male and female rats [P < 0.05], but no sex difference was detected. The renal vasculature of male rats may provide more response to Ang II administration-induced NO, which is dependent on masR and AT2R. During dual masR + AT2R blockades, the kidney NO formation wasreduced in a non-gender related manner

Serum and peritoneal fluid levels of vascular endothelial growth factor in women with endometriosis

Endometriosis is known as one of the most common disease in women of reproductive age. Due to important role of vascular endothelial growth factor [VEGF] in neo-vascularization for the implantation of endometrial cell, and also presence of different studies reported VEGF level in the serum and peritoneal fluid [PF] in endometriosis patients, this study was designed to determine the serum and PF levels of VEGF in endometriosis patients, and to compare with normal subjects. In this descriptive study, 179 women subjected to laparoscopy for the evaluation of infertility or pelvic pain were allocated into the following two groups: group I: different types of endometriosis patients [n=90] and group II: non-endometriosis patients [n=89]. The PF from pelvis and venous blood samples were obtained. The VEGF concentration of the serum and PF were measured using enzyme immunoassay kit and were compared using t test. The level of VEGF in serum was significantly less than that in PF in both groups [p=0.00]. However, endometriosis patients had significantly higher level of VEGF in peritoneal fluid than non-endometriosis patients [p=0.043]. According to our findings, endometriosis is not associated with change in the level of circulating VEGF

role of magnesium supplementation in cisplatin-induced nephrotoxicity in a rat model: no nephroprotectant effect

Cisplatin [CP] is used as the commonest drug to treat solid tumors. It is accompanied by a nephrotoxicity side effect. The main objective of this study is to investigate the protective role of magnesium [Mg] supplementation in CP-induced nephrotoxicity in a rat model. Twenty-nine Wistar rats were randomly assigned to four groups [1-4]. Groups 1-3 received 20, 80, and 200 mg/kg magnesium sulfate respectively, for 10 days, but on day 3, a single dose of CP [7 mg/kg, i.p.] was also injected. Group 4 [positive control group] received the same regimen of Groups 1-3 except saline instead magnesium sulfate. One week after CP administration, blood samples were obtained and all animals were killed for kidney histopathological investigations. All CP-treated animals lost weight, and the percentage of weight loss in Group 1 [low dose Mg sulfate treated] was significantly higher compared with the positive control group [Group 4, P < 0.05]. The increase in blood urea nitrogen [BUN] and creatinine [Cr] levels in serum in Group 1 were more than those in other groups [P < 0.05]. No statistical differences were observed in serum magnesium, nitrite, and total protein levels among the groups. The kidney tissue damage in Groups 1-3 was not significantly different when compared with Group 4. Moreover, the kidney and testis weights in Group 1 were significantly greater than those in the positive control group [P < 0.05]. Regarding the BUN and Cr levels in the serum, kidneys weight, and the histopathological study, the low dose of Mg supplementation intensifies kidney toxicity and renal dysfunction in CP-induced nephrotoxicity in the rat model. However, the protective role of Mg with moderate and high doses is not certain