Potential antidotal effect of naloxone against captopril acute toxicity in albino rats

Captopril, is an angiotensin converting enzyme inhibitor which is widely used in the management of hypertension, has many new potential applications opening the way for wider deployment. Naloxone which is an opioid antagonist was reported to block the inhibitory effect of B-endorphin on the centrally mediated pressure action of angiotensin II thus reversing hypotension. This work aimed at evaluating the acute toxic effects of captopril and to detect the potential protective role of naloxone in ameliorating this toxicity. Seventy adult albino rats of both sexes were divided into 7 equal groups. Group [I]. [II] and [III: negative and positive control groups. Group [IV] [Naloxone group]: naloxone was given in a single I.P dose of 0.06mg/rat. Group [V] [Captopril group,: Captopril was given in a single toxic oral dose of 13.5mg/rat. Group [VI] [Captopril and Naloxone]: a single I.P dose of naloxone [0.06mg/rat] was given 1 hour after captopril single oral toxic dose. Group [VII]: A single I.P dose of naloxone [0.06mg/rat] was given 2 hours after captopril single oral toxic dose. After 24 hours from naloxone intake. the animals were anaesthesized, blood pressure and pulse rate were measured after aortic exposure. Then the animals were sacrificed and blood samples were collected for investigating liver function tests, kidney function tests and serum electrolytes. Liver and kidney specimens were also examined histologically. It was found that captopril significantly decreased the blood pressure but did not affect pulse rate. Captopril also significantly affected the liver function tests. kidney function tests, and serum electrolytes. The administration of naloxone 1 hour and 2 hours after captopril significantly improved blood pressure, liver function tests, kidney function tests and serum electrolytes There was non significant difference between the administration of naloxone 1 hour or 2 hours after captopril. The biochemical results were coinciding with the histological results. So, naloxone was found to have an antidotal effect against captopril toxicity. The very common use of captopril in medical practice, together with the severity of the toxicity, may cause calls for increased awareness and an antidotal management

Muscular and haematopoietic toxicities of zidovudine in adult albino rat. Evaluation of the possible role of some antioxidants

Zidovudine, a potent inhibitor of retroviral replication was the first drug approved for the treatment of Acquired Immunodeficiency Syndrome [AIDS]. Long term use of Zidovudine in patients with AIDS is frequently associated with periods of dose reduction or discontinuation of therapy due to the development of muscular and haematopoietic toxicities. Zidovudine toxicity is thought to be mediated through its action on mitochondria with increased reactive species and oxidative DNA damage. Some antioxidants [Vitamin C, Zinc and N-acetyl Cysteine] were tried in this work aiming to evaluate their possible protective effects on zidovudine - induced muscle and haematopoietic toxicities. One hundred and eighty adult albino rats of both sexes were used in this study divided equally into the following groups: Group I: was considered as -ve control group. Group II: animals received distilled water orally: Group III: in which animals received vitamin C orally at a dose of 175 mg/day. Group IV included animals which received Zinc Oxide orally at a dose of 6 mg/day. Group V: in which animals received N-Acetyl Cysteine [NAC] orally at a dose of 18 mg/day. The drugs used in Group III, IV, V were given for 50 consecutive days. Group VI: included animals which receive Zidovudine [AZT] in a dose of [10.8 mg/rat] oraly for 35 consecutive days. Group VII: comprise animals which were pretreated with vitamin C for 15 days, then vitamin C was given concomitant with AZT for 35 consecutive days at the same previously given dose and route for each. Group VIII: In which animals received Zinc Oxide before AZT for 15 days then Zinc Oxide concomitant with AZT for 35 consecutive days at the same previously given dose and route for each. Group IX comprised animals which received NAC for 15 consecutive days before then concomitant with AZT for 35 consecutive days at the same previously given dose and route for each. At the end of the experiment blood samples used for blood count were collected. Aliquots of the samples were centrifuged and the plasma was used for determination of serum malondialdehyde [MDA] level. Animals were sacrificed and the heart and gastrocnemius muscle with related bone were prepared for histological examination. In AZT group there was marked decrease in total WBC count, RBC count and platelet count with significant increase in serum MDA level. The L/M examination of skeletal and cardiac muscle sections revealed focal areas of necrosis with complete loss of architecture together with mononuclea; cellular infiltration. Skeletal muscles of the same group showed focal depletion of sarcoplasmi, PAS positive material and mitochondrial content together with increase in collagen fiber deposition. E/M examination of cardiac myocytes showed abundant sarcoplasmic vacuolation and myofibrillar loss. Their mitochondria showed different grades of degenerative changes. The bone marrow sections of AZT group showed marked hypercellularity, decrease bone marrow vacuolar spaces, dilated congested blood sinusoids. In AZT and vitamin C group [VII] and AZT with Zinc group [VIII] there was marked elevation of all blood count with marked drop in the level of serum MDA compared with AZT group. Also nearly complete normalization of the histological profile of skeletal and cardiac muscle was obtained in the same groups. The bone marrow sections of AZT and vitamin C group was nearly similar to - ve control group while that of AZT + Zinc group still showed changes. Whereas there was mild improvement of the skeletal, cardiac muscle and bone marrow AZT - induced histological and biochemical changes was detected in AZT and NAC group [IX]

Correlation between timing of wounds and the level of soluble intercellular adhesion molecule type 1 [sICAM-1] in traumatized individuals

Cytokines are important in the control of wound healing. Many cytokines could be useful for the determination of wound age. The most important of these cytokines are the growth factors and adhesion molecules. Thirty traumatized individuals of both sexes were subjected to this study and were divided, according to the degree of injury severity score [ISS], into three groups; mild, moderate and severe trauma groups; each group consisted of ten patients. Each group is consisted of ten patients. Each group is further subdivided, according to sampling time, into three subgroups: within the 1[st] 24 hours of admission, on the third day, and on the fifth day of admission. The control group consisted of six persons. The present study was conducted to correlate between the level of the soluble intercellular adhesion molecule type-1 [sICAM-1] and the timing of wounds in traumatized individuals. The level of sICAM-1 was measured in plasma using the ELISA technique and was estimated in relation to the time passed since infliction of injury on the 1[st] day of admission, on the 3[rd] day and on the 5[th] day. A significant increase was noticed in all subgroups when compared with the control group. A characteristic pattern of sICAM-1 variation with the timing of wounds was at its maximum level on the 3[rd] day post-trauma and then decreases towards its normal level. A number of factors were also compared with the sICAM-1 level and these included the nature of injury, the associated severe head injuries, and the combing bone affection with the soft tissue injuries. All the previously mentioned factors in the present work did not affect the characteristics pattern of sICAM-1 variation with the timing of wounds. Furthermore, sICAM-1 level was found to be significantly correlated with the degree of injury severity. It is recommended to use sICAM-1in the estimation of the timing of wounds in traumatized individuals

Effect of zidovudine an anti-human immune deficiency virus [HIV] on skeletal and cardiac muscles of adult albino rat. evaluation of the possible role of some antioxidants

Antiretroviral agents are the cornerstone in the management of Human Immunodeficiency Virus [HIV]. Zidovudine, a potent inhibitor of retroviral replication was the first drug approved for the treatment of Acquired Immunodeficiency Syndrome [AIDS]. Long term use of zidovudine in patients with AIDS is frequently associated with periods of dose reduction or discontinuation of therapy due to the development of muscular toxicity. Zidovudine toxicity is thought to be mediated through its action on mitochondria with increased reactive species and oxidative DNA damage. Some antioxidants [vitamin C, zinc and N-acetyl cysteine] were tried in this work aiming to evaluate their possible protective effects on zidovudine-induced muscle toxicity. Forty eight adult albino rats of both sexes were used in this study divided equally into the following groups: group I was considered as a control group. Group II in which animals received vitamin C orally at a dose of 175mg/day. Group III included animals which received zinc oxide orally at a dose of 6 mg/day. Group IV in which animals received N-acetyl cysteine [NAC] orally at a dose of 18 mg/day. The drugs used in groups II, III and IV were given for 50 consecutive days. Group V included animals which received zidovudine [AZT] in a therapeutic dose [10.8 mg/rat] orally for 35 consecutive days. Group VI comprised animals which were pretreated with vitamin C for 15 days then vitamin C was given concomitantly with AZT for 35 consecutive days at the same previously given dose and route for each. Group VII in which animals were pretreated with zinc oxide for 15 days then zinc oxide was given concomitantly with AZT for 35 consecutive days at the same previously given dose and route for each. Group VIII comprised animals which received NAC for 15 consecutive days then it was given concomitantly with AZT for 35 consecutive days at the same previously given dose and route for each. At the end of the experiment blood samples were collected for detection of serum malondialdehyde [MDA] level, animals were sacrificed and the heart and gastrocnemius muscle were prepared for histological examination. In AZT group the L/M examination of skeletal and cardiac muscle sections revealed focal areas of necrosis with complete loss of architecture together with mononuclear cellular infiltration. Skeletal muscles of the same group showed focal depletion of sarcoplasmic PAS positive material and mitochondrial content and increase in collagen fiber deposition. E/M examination of cardiac myocytes showed abundant sarcoplasmic vacuolation and myofibrillar loss. Their mitochondria showed different grades of degenerative changes in the form of disrupted cristae, focal areas of matrical loss and ruptured membrane. Marked elevation of the level of serum malondialdehyde [MDA] was also detected. Nearly complete normalization of the histological profile of the skeletal and cardiac muscle was obtained in AZT and vitamin C group [VI] and AZT and zinc group [VII] as well as marked drop in the level of serum [MDA]. Meanwhile, mild improvement of the skeletal and cardiac muscle AZT-induced histological and biochemical changes was detected in AZT and NAC group [VIII]

Importance of nucleophilic thiols in modulating cyclophosphamide toxicity on the heart, urinary bladder and bone marrow of adult albino rats

Cyclophosphamide [CPH] is a synthetic antineoplastic agent, N-acetyl cysteine [NAC] and mesna [sodium 2 mercaptoethane sulphonate] are two members of the nucleophilic thiols. One hundred adult albino rats were used in this study. They were calssified into 10 equal groups. Groups I, II and III were control groups [-ve and +ve controls]. Group IV: [Mesna alone]. The animals of this group received 4 doses of Mesna each of 25mg/kg I.P for 5 days as follows: the 1[st] dose was given followed by the 2[nd] dose after 1/3 of an hour, then the 3[rd] dose was given after 3 hours followed by the 4[th] dose after another 3 hours. Group [V] [NAC alone]: the animals of this group received NAC at a dose of 100 mg/kg orally for 5 days. Group [VI] [Mesna and NAC]: the animals of this group received 4 doses of mesna and one dose of NAC concomitantly with the 2[nd] dose of mesna for 5 days following the same regimen and dose for each. Group [VII] [CPH alone]: the animals of this group received cyclophosphamide in a dose of 50 mg/kg I.P for 5days. Group [VIII] [CPH and Mesna]: the animals received 4 doses of mesna. CPH was given concomitantly with the 2[nd] dose of mesna. Both were given at the same previously mentioned doses and routes for 5 days. Group [IX] [CPH and NAC]: the animals received CPH concomitantly with NAC at the same previously mentioned doses and routes for 5 days. Group [X] [CPH, mesna and NAC]: the animals of this group received 4 doses of mesna. CPH and NAC were given concomitantly with the 2[nd] dose of mesna. All were given at the same previously mentioned doses and routes for each for 5 days. Animals of all groups were sacrificed 24 hours after the last dose. Blood samples were collected for investigating complete blood count [CBC], serum lactic dehydrogenase [LDH] and creatine phosphokinase [CPK] enzymes. Heart, urinary bladder and bone marrow were examined both histologically and histochemically. Cyclophosphamide significantly reduced the total leukocytic count [TLC], platelet count, hemoglobin concentration and lymphocytic count and increased the blood levels of LDH and CPK enzymes. Histologically CPH caused focal areas of cardiac necrosis, intramyocardial hemorrhage and Dilated, congested blood vessels. Whereas, it caused urinary bladder mucosal ulceration, interstitial edema and congestion with mononuclear cellular infiltration. Bone marrow hypocellularity, undifferentiated leukocytic series were also noticed in CPH group. Concomitant administration of mesna recovered completely the CPH-induced urinary bladder toxicity. However, it didn't improve either the blood picture or the cardiac enzymes and didn't recover completely neither the hemopoietic nor the cardiac toxicity of CPH. Whereas, concomitant administration of NAC or NAC and mesna with CPH improved completely the CPH induced hemopoietic and cardiac toxicity as indicated biochemically and histologically and to lesser extent the urinary bladder toxicity. So, it is recommended to prescribe NAC and mesna together with alkylating agents particularly cyclophosphamide to modulate its toxicity