Evaluating the effects of rifampin in the prevention of neurogenic symptoms and cardiac arrhythmias caused by the systemic toxicity of lidocaine in rats.

Lidocaine toxicity is caused by unintended intravascular injection or overdose. Lidocaine is metabolized in the liver by the CYP3A4 isoenzyme. The objective was to investigate if the administration of rifampin could accelerate animal recovery and reduce the symptoms of lidocaine toxicity by induction of the CYP3A4. Thirty-six male rats were divided into control and treatment groups, each containing three subgroups. The treatment group received oral rifampin suspension daily for 1 week. In all rats, 2.00% lidocaine was injected intravenously. The first subgroup was monitored for neurological symptoms. In the second subgroup, data were recorded after the electrode was placed in the right hippocampus. Electrocardiograms were taken from the third subgroup. CYP3A4 was measured using an ELISA kit. Neurological recovery was seen after 22 and 15 min in the control and treatment groups, respectively. Rifampin also caused a significant reduction in amplitude and number of field action potentials compared to the control group. Numerous cardiac arrhythmias were observed in the control group. The mean level of CYP3A4 in the treatment group was significantly higher than in the control group. In conclusion, oral rifampin could increase the synthesis of CYP3A4, therefore, the animal recovery from lidocaine toxicity was accelerated.

Effects of adenosine N1-Oxide and pioglitazone on inflammatory and antioxidant state in sepsis caused by experimental cecal puncture in rat.

Sepsis is an acute condition caused by the systemic inflammatory response syndrome to an infection. There are very few drugs that could improve the severe conditions in patients with sepsis. Hence, it is important to consider different treatment options. In this survey, we studied the effect of adenosine N1-oxide (ANO) and pioglitazone on rats with cecal ligation and perforation (CLP). They were randomly divided to four groups (n = 10) including Group A: as control group receiving normal saline, Group B: the rats with CLP as surgical control group, Group C: the rats receiving ANO, and Group D: the rats receiving pioglitazone. Interleukin (IL) -6, IL-1ß, tumor necrosis factor alpha (TNF-α), nitric-oxide (NO) in serum blood and superoxide dismutase (SOD), catalase (CAT) malondialdehyde, (MDA) and myeloperoxidase (MPO) in liver and spleen homogenates were measured. The amount of antioxidant enzymes in the spleen and liver, and finally cell viability and rats' survival were investigated. The measurement of blood serum nitric-oxide and survival of all groups of rats were also performed. The results indicated that both drugs could cause a decrease in IL-1ß, IL-6, TNF-α and NO in rat blood serum and MDA and MPO in the liver and spleen homogenates, however, a significant increase in SOD and CAT in the liver and spleen homogenates in rats that received ANO and pioglitazone was observed compared to rats with CLP group. Cell viability and rats' survival were significantly improved in rats that received ANO and pioglitazone compared to rats with CLP group. Adenosine N1-oxide showed stronger and more effective effects.

Lycopene improves testicular damage and sperm quality in experimentally induced varicocele: Relationship with apoptosis, hypoxia, and hyperthermia.

Varicocele is considered the main reason for male infertility. Antioxidants are common drugs used to reduce the complications of varicocele in these patients. So, we investigated the effects of lycopene on sperm quality, testicular histology, and the expression of some genes in experimentally induced varicocele. Fifty adult male Wistar rats were divided into three groups: control (n = 12), sham (n = 5), and varicocele (n = 33) groups. After 2 months of induced varicocele, five rats were randomly sacrificed and induced varicocele was investigated in each group. Finally, 35 rats were divided into five groups: the control, varicocele, varicocele reserving solvent, and varicocele reserving lycopene (4 and 10 mg/kg) for 2 months. At the end of the experiment, sperm viability, membrane integrity, the expression of Bax, Bcl2, hypoxia (hypoxia-inducible factor 1α [HIF1-α]), heat-shock protein (heat-shock protein A2 [HSPA2]) genes, and the histology of testes were measured. The results showed a significant decrease in the sperm viability, membrane integrity, Johnson's score, and the expression of the Bcl2 gene in the varicocele group compared to the control group. Also, there was a significant increase in Bax, HSPA2, and HIF1-α expressions in the varicocele group compared to the control group. Although the administration of lycopene (10 mg/kg) in rats with varicocele improved sperm viability and membrane integrity, Johnson's score, and Bax expression compared to the varicocele group. Our findings indicated that the administration of lycopene in the varicocele group improved sperm quality and testicular injury induced by varicocele via decreasing apoptosis.

Lycopene protects sperm from oxidative stress in the experimental varicocele model.

Oxidative stress (OS) is an important parameter in the evaluation of infertility caused by varicocele. Antioxidants are the most commonly prescribed drugs in these patients. Lycopene molecule, as the powerful antioxidant in the carotenoid family, has beneficial effects on improving fertility in males. Therefore, we investigated the effects of lycopene on induced OS by varicocele in an animal model. Forty-five adult male Wistar rats were divided into two groups: control (n = 12) and varicocele (n = 33). Two months after induced varicocele, five rats in each group were sacrificed randomly and induced varicocele was investigated. Remained rats were divided into five groups (n = 7), including the control (I), varicocele (II), varicocele reserving solvent (III), varicocele reserving lycopene 4 mg/kg (IV), and 10 mg/kg (V) for two months. At the end of the experiment, intracellular reactive oxygen species (ROS), malondialdehyde (MDA), total antioxidant capacity (TAC), %DNA damage, and antioxidant enzymatic levels were measured. The results indicated that there were significant increases in the levels of ROS, MDA, DNA damage, superoxide dismutase (SOD), sperm concentration, and motility in the varicocele groups compared with the control group. In the lycopene group (10 mg/kg), sperm concentration, the levels of TAC, and catalase (CAT) activity were improved so the levels of ROS, MDA, and %DNA damage were reduced compared with varicocele group. Our findings indicated that the administration of lycopene especially at a dose of 10 mg/kg in the varicocele group could protect sperm from OS and sperm DNA damage by increasing antioxidant activity and reducing ROS.

Comparison of Anesthetic Efficacy of Lidocaine and Bupivacaine in Spinal Anesthesia in Chickens.

Lidocaine is used for epidural and spinal anesthesia in various animal species. The ideal drug for epidural and spinal anesthesia should have a long effective duration in addition to a fast onset of action, and adequate analgesia and muscle relaxation. Despite the delayed onset of action, bupivacaine provides a longer duration of anesthesia than lidocaine. The purpose of this study was to compare the onset to effect and duration of action between lidocaine and bupivacaine for spinal anesthesia in broiler chickens. Thirty-two, 8-week-old, female Ross broiler chickens were randomly divided into 4 groups of 8: 1) 2 mg/kg lidocaine (L); 2) 0.1 mg/kg bupivacaine (B0.1); 3) 0.25 mg/kg bupivacaine (B0.25); and 4) 0.5 mg/kg bupivacaine (B0.5). After aseptic preparation, a 23-gauge spinal needle was inserted into the synsacrococcygeal space of the chickens with correct needle placement confirmed by a sudden loss of resistance. Spinal anesthesia was performed with the aforementioned doses of lidocaine and bupivacaine. The respiratory rate and cloacal temperature were measured every 10 minutes in each chicken until the anesthetic effect was no longer present. The onset to effect and the duration of action were calculated for each bird based on the pinch test at predetermined time intervals. The results are demonstrated as mean ± SD. The onset of action for bupivacaine (9 ± 1.41, 4.33 ± 1.15, and 3.33 ± 1.23 minutes in B0.1, B0.25, and B0.5 groups, respectively) was significantly delayed compared with that of lidocaine (1.37 ± 0.52 minutes). The duration of action of B0.5 (54 ± 6.08 minutes) was significantly longer than that of any other group (17.87 ± 3.18, 11 ± 1.41, and 18 ± 4.36 min in L, B0.1, and B0.25 groups, respectively). The results showed that a spinal injection of 0.5 mg/kg bupivacaine produces approximately 55 minutes of spinal anesthesia in these broiler chickens, which is much longer than the 18 minutes of anesthesia provided by 2 mg/kg lidocaine. Considering the various disease conditions that affect the cloacal area of birds, one can use each of these anesthetic drugs for either short-term or long-term spinal anesthesia in chickens and possibly other avian species.

The Roles of Lactobacillus Acidophilus and Pectin in Preventing Postoperative Sepsis and Intestinal Adaptation in a Rat Model of Short Bowel Syndrome.

One of the primary causes of morbidity and mortality in those with short bowel syndrome (SBS) is sepsis, caused by bacterial translocation (BT). Since synbiotics can cease gut-related bacterial overgrowth, they may serve as a supportive dietary supplement-based strategy after gastrointestinal surgery. This study was conducted to determine the effects of Lactobacillus acidophilus and pectin on BT and gut adaptation after extensive small bowel resection in the rat. Forty rats were distributed in four groups. Group A suffered laparotomy, group B suffered gut transection and reanastomosis, SBS rats (group C) suffered 75% small gut resection, and finally, Group D suffered gut resection and treated with a synbiotic cocktail from day 7 before the surgery to day 14 after it. Intestinal structural changes and BT to mesenteric lymph nodes, liver, portal blood, and peripheral blood were detected on day 15 post-surgery. Treatment with a synbiotic cocktail led to a considerable reduction in bacterial translocation to liver and portal vein (degree II) compared with SBS untreated rats. Also, synbiotic administration significantly increased jejunum and ileum villus height and crypt depth, ileum villus width, and percentage of goblet cells in jejunum and ileum compared with SBS rats. In the rat model of short bowel syndrome, L. acidophilus, and pectin, as a potential synbiotic compound, could decrease the BT from the gut and improve the bowel adaptation.

Evaluation of magnesium sulfate effects on fetus development in experimentally induced surgical fetal growth restriction in rat.

Objective: The objective of this study was to evaluate the effect of magnesium sulfate in the prevention of fetal growth restriction due to the impaired uterine blood supply in the rat model.Methods: A total number of 24 female rats were used in this study. They were mated overnight and randomly divided into control and treatment groups. After anesthesia and incising abdominal midline in day 17 of gestation, the uterine artery was occluded by an atraumatic clamp for 60 min. The rats of the control group received normal saline after surgery and the rats of treatment group received magnesium sulfate subcutaneously. The laparotomy was repeated on day 21 of gestation, and the number of alive and dead fetuses was counted in each horn. The viability of fetuses was evaluated. The weight of the placenta and fetuses and the distance between the head and tail as well as back to the abdomen of the fetuses were also measured. Samples of the amniotic fluid (AF) were collected during both surgeries for biochemical analyses of the glucose, urea, lactate, and pyruvate levels by an AutoAnalyzer.Results: Among the total fetuses in ischemic horn, only 50% survived in the control group. Dead fetuses had less body consistency and had a dark color. In contrary, only 7.6% of the fetuses in the treatment group were absorbed and 92.4% were completely healthy and developed. Parameters related to placenta weight, fetus weight, fetus length, and fetus width had significant differences and those of the treatment group were higher. Glucose and lactate levels of the AF in the treatment group were significantly lower and urea level was significantly higher than the control group in day 21 of gestation. The changes in pyruvate levels were not significant.Conclusion: In conclusion, magnesium sulfate may counteract with the effects of temporary uterine ischemia in pregnant rats and prevent intrauterine growth restriction.

Curcumin and Nanocurcumin Oral Supplementation Improve Muscle Healing in a Rat Model of Surgical Muscle Laceration.

OBJECTIVE: To compare the effects of curcumin and nanocurcumin oral supplementation on the muscle healing rate of an animal model of surgical muscle laceration. METHODS: Thirty-two male adult rats were randomly divided into sham, control, curcumin, and nanocurcumin groups. Partial transection of the gastrocnemius muscle was made in the right limb of the control and treatment groups. The sham and control groups received normal saline, curcumin group received 500 mg/kg of curcumin and nanocurcumin group received 100 mg curcumin-loaded nanomicelles orally every day. They euthanized two weeks later and the specimens were stained by hematoxylin-eosin (H&E) and Masson's trichrome methods. Aspartate transaminase (AST) and creatine phosphokinase (CPK) were measured in blood samples. RESULTS: The percentage of collagen fibers in the nanocurcumin group was significantly lesser than the control and curcumin groups (p<0.001). Muscle fiber regeneration in the treatment groups was significantly higher than the control group (p<0.001). The blood vessels of the nanocurcumin group were significantly more than other groups (p<0.001). Plasma AST had a significant difference in the control group compared to the sham and nanocurcumin groups (p=0.026). The plasma CPK level of the control group was also significantly higher than other groups (p<0.001). CONCLUSION: In conclusion, although oral curcumin supplementation has little effects because of its poor bioavailability, embedding it in nanoparticles could enhance its systemic effects in promoting the muscle healing process.

Effects of L-carnitine and betamethasone on ischemia-reperfusion injuries and sperm parameters following testicular torsion in a rat model.

Testicular torsion is a consequence of spermatic cord twisting which causes progressive damage to the structure of the testis and reduces sperm quality and usually results in infertility. In the present study, with the assumption of the protective effects of L-carnitine and betamethasone against ischemia-reperfusion (IR) injuries, their effects on twisted testicles were evaluated and compared. Twenty Wistar rats were randomly divided into four groups and used in this study. Except for the Sham (S) group, testicular IR was induced surgically in three other groups, including Control (C), Betamethasone (BM), and L-carnitine (LC) groups. Betamethasone and L-carnitine were injected before detorsion in the BM and LC groups, respectively. After twelve hours of reperfusion, the testicles were detached, and prepared for sperm parameters evaluation such as sperm count, motility, viability, morphology, and chromatin quality, and histopathologic evaluations, including mean seminiferous tubular diameter (MSTD), germinal epithelial cell thickness (GECT), and Johnsen's mean testicular biopsy scoring (MTBS). The MSTD, GECT, and healthy sperms in the C group were significantly lower than the other groups, while the BM and LC groups were significantly different from others in MTBS. The number of sperms and sperm motility in the BM group was significantly higher than the C group. Sperm viability in the BM and LC groups were significantly higher than the C group. The results of this study showed that both L-carnitine and betamethasone similarly can be effective in treating testicular IR injuries.

Allogenous skin fibroblast transplantation enhances excisional wound healing following alloxan diabetes in sheep, a randomized controlled trial.

BACKGROUND: Healing of skin wound is a multi-factorial and complex process. Treatment of diabetic wounds is still a major clinical challenge. Recently, stem cell transplantation to chronic wounds is favored. The objective of this study was to evaluate effects of pre-labeled allogenous skin fibroblasts on healing of ovine diabetic wound model. METHODS: Eight 4-month-old Iranian Makoui wethers were used in this study. Alloxan monohydrate was used for induction of diabetes. In each wether two excisional wound were created on dorsum of the animal. Wounds of one side were randomly chosen as treatment group (n = 8), and wounds of the other side were considered as control group (n = 8). Pre-labeled skin fibroblasts with bromodeoxyuridine were used in wounds of one side as treatment. Photographs were taken in distinct times for planimetric evaluation. Wound samples were taken for BrdU detection and histopathologic evaluations on day 21 post-wounding. RESULTS: The planimetric study showed closure of fibroblast treated wounds is significantly faster than control group (P < 0.05). Immunohistochemical staining with anti-bromodeoxyuridine antibody indicated presence of transplanted cells in the wounds. Histopathologic evaluations of H&E stained sections disclosed significantly increasing of re-epithelialization, number of fibroblasts, and number of blood vessels in treatment group in comparison to control group (P < 0.05). CONCLUSION: [corrected] The results of this study indicated that allogenous skin fibroblast transplantation can positively affect wound healing in diabetic sheep.

Healing of excisional wound in alloxan induced diabetic sheep: A planimetric and histopathologic study.

Healing of skin wound is a multi-factorial and complex process. Proper treatment of diabetic wounds is still a major clinical challenge. Although diabetes mellitus can occur in ruminants, healing of wounds in diabetic ruminants has not yet been investigated. The aim of this study was to evaluate healing of ovine excisional diabetic wound model. Eight 4-month-old Iranian Makoui wethers were equally divided to diabetic and nondiabetic groups. Alloxan monohydrate (60 mg kg(-1), IV) was used for diabetes induction. In each wether, an excisional wound was created on the dorsum of the animal. Photographs were taken in distinct times for planimetric evaluation. Wound samples were taken on day 21 post-wounding for histopathologic evaluations of epidermal thickness, number of fibroblasts and number of new blood vessels. The planimetric study showed slightly delay in wound closure of diabetic animals, however, it was not significantly different from nondiabetic wounds (p ≥ 0.05). Furthermore, epidermal thickness, number of fibroblasts and number of blood vessels were significantly lower in diabetic group (p < 0.05). We concluded that healing of excisional diabetic wounds in sheep may be compromised, as seen in other species. However, contraction rate of these wounds may not be delayed due to metabolic features of ruminants and these animals might go under surgeries without any serious concern. However, healing quality of these wounds may be lower than normal wounds.