Administration Of Cimetidine Research Articles

Susceptibility of mouse cochlear hair cells to cisplatin ototoxicity largely depends on sensory mechanoelectrical transduction channels both Ex Vivo and In Vivo

Cisplatin, a highly effective chemotherapeutic drug for various human cancers, induces irreversible sensorineural hearing loss as a side effect. Currently there are no highly effective clinical strategies for the prevention of cisplatin-induced ototoxicity. Previous studies have indicated that short-term cisplatin ototoxicity primarily affects the outer hair cells of the cochlea. Therefore, preventing the entry of cisplatin into hair cells may be a promising strategy to prevent cisplatin ototoxicity. This study aimed to investigate the entry route of cisplatin into mouse cochlear hair cells. The competitive inhibitor of organic cation transporter 2 (OCT2), cimetidine, and the sensory mechanoelectrical transduction (MET) channel blocker benzamil, demonstrated a protective effect against cisplatin toxicity in hair cells in cochlear explants. Sensory MET-deficient hair cells explanted from Tmc1Δ;Tmc2Δ mice were resistant to cisplatin toxicity. Cimetidine showed an additive protective effect against cisplatin toxicity in sensory MET-deficient hair cells. However, in the apical turn, cimetidine, benzamil, or genetic ablation of sensory MET channels showed limited protective effects, implying the presence of other entry routes for cisplatin to enter the hair cells in the apical turn. Systemic administration of cimetidine failed to protect cochlear hair cells from ototoxicity caused by systemically administered cisplatin. Notably, outer hair cells in MET-deficient mice exhibited no apparent deterioration after systemic administration of cisplatin, whereas the outer hair cells in wild-type mice showed remarkable deterioration. The susceptibility of mouse cochlear hair cells to cisplatin ototoxicity largely depends on the sensory MET channel both ex vivo and in vivo. This result justifies the development of new pharmaceuticals, such as a specific antagonists for sensory MET channels or custom-designed cisplatin analogs which are impermeable to sensory MET channels.

Effect of Cimetidine on Metformin Pharmacokinetics and Endogenous Metabolite Levels in Rats.

Tubular secretion is a primary mechanism along with glomerular filtration for renal elimination of drugs and toxicants into urine. Organic cation transporters (OCTs) and multidrug and toxic extrusion (MATE) transporters facilitate the active secretion of cationic substrates, including drugs such as metformin and endogenous cations. We hypothesized that administration of cimetidine, an Oct/Mate inhibitor, will result in increased plasma levels and decreased renal clearance of metformin and endogenous Oct/Mate substrates in rats. A paired rat pharmacokinetic study was carried out in which metformin (5 mg/kg, intravenous) was administered as an exogenous substrate of Oct/Mate transporters to six Sprague-Dawley rats with and without cimetidine (100 mg/kg, intraperitoneal). When co-administered with cimetidine, metformin area under the curve increased significantly by 3.2-fold, and its renal clearance reduced significantly by 73%. Untargeted metabolomics was performed to investigate the effect of cimetidine on endogenous metabolome in the blood and urine samples. Over 8,000 features (metabolites) were detected in the blood, which were shortlisted using optimized criteria, i.e., a significant increase (P value < 0.05) in metabolite peak intensity in the cimetidine-treated group, reproducible retention time, and quality of chromatogram peak. The metabolite hits were classified into three groups that can potentially distinguish inhibition of i) extra-renal uptake transport or catabolism, ii) renal Octs, and iii) renal efflux transporters or metabolite formation. The metabolomics approach identified novel putative endogenous substrates of cationic transporters that could be tested as potential biomarkers to predict Oct/Mate transporter mediated drug-drug interactions in the preclinical stages. SIGNIFICANCE STATEMENT: Endogenous substrates of renal transporters in animal models could be used as potential biomarkers to predict renal drug-drug interactions in early drug development. Here we demonstrated that cimetidine, an inhibitor of organic cation transporters (Oct/Mate), could alter the pharmacokinetics of metformin and endogenous cationic substrates in rats. Several putative endogenous metabolites of Oct/Mate transporters were identified using metabolomics approach, which could be tested as potential transporter biomarkers to predict renal drug-drug interaction of Oct/Mate substrates.

Hypocalcemic tetany associated with simultaneous administration of cimetidine and nifedipine: a case report

BackgroundAcute hypocalcemia is generally caused by a sudden drop in serum calcium ion and presents with a mild or severe form of tetany. Even though the occurrence of hypocalcemia is well documented with certain drugs such as calcium chelators, bisphosphonates, and cisplatin, it is a very unusual and poorly documented adverse event with cimetidine and nifedipine. Here, we present a case of severe hypocalcemic tetany during simultaneous administration of cimetidine and nifedipine in a hypertensive patient with dyspepsia.Case presentationA 46-year-old known human immunodeficiency virus patient from Ethiopia on antiretroviral therapy over the past 14 years presented to the emergency department with acute exacerbation of dyspepsia and hypertensive urgency. She was given intravenous cimetidine (400 mg) and oral nifedipine (30 mg) simultaneously. One hour after the administration of these two drugs, she developed severe hypocalcemic tetany with carpopedal spasm, involuntary plantar flexion, and muscle spasms. She also had severe retrosternal chest pain and shortness of breath. Her blood pressure was 160/110 mmHg during the attack and she had no skin changes, such as urticaria. She was immediately given 1 g of calcium gluconate intravenously over 30 minutes. The carpopedal spasm progressively decreased during calcium gluconate administration. An hour later, she completely regained voluntary movement of her fingers and feet. The chest pain persisted, but resolved over the next 12 hours. The patient was discharged home after 2 days of observation. This is an unusual adverse effect that needs caution during concomitant administration of these drugs.ConclusionsSevere hypocalcemic tetany can occur with concomitant administration of cimetidine and nifedipine. Immediate treatment with calcium gluconate quickly reverses this adverse event. Concomitant administration of these drugs should be done with caution or be avoided if possible.

The role of Cola nitida on gastric acid secretion and its mechanism of action in male Wistar rats

This study investigated the effect of an aqueous extract of Cola nitida (AECN) and decaffeinated (DECAF) extract of kolanut on gastric acid secretion and its mechanism of action in rats. Previous reporters only speculated that the biological effect of kolanut in causing gastric acid secretion could be ascribed to its caffeine content, also the mechanism is not fully elucidated. In addition, none of the previous reporters has investigated the effect of decaffeinated kolanut extract on gastric acid secretion. Sixty (60) male adult Wistar rats divided into twelve groups of five rats each were used for this study. Groups 1 and 2 received normal saline orally and intravenously respectively at a dose of (1 ml/kg), 3 and 4 received 25 mg/kg of (AECN) orally and intravenously respectively, group 5 received (100mg/kg) AECN orally, groups 6 and 7 received 25mg/kg of (DECAF) both orally and intravenously respectively, group 8 received 100mg/kg of DECAF orally, groups 9 and 10 were pre-treated with cimetidine 12 μmoles/kg intravenously followed by 25 mg/kg AECN and DECAF respectively, groups 11 and 12 were pre-treated with i.v atropine (0.2 mg/kg) followed by 25 mg/kg of AECN and DECAF respectively. Gastric acid secretion was determined by continuous perfusion of rats' stomachs under urethane anesthesia. Data collected were expressed as mean ± SEM. Statistical significance at P≤0.05 was determined using Student’s t-test analysis. The oral administration of AECN (25mg/kg and 100mg/kg) and i.v AECN (25mg/kg) caused a significant increase (P≤0.05) in gastric acid secretion (GAS) with pronounced effect than DECAF group. The oral administration of 25mg/kg and 100mg/kg of DECAF and intravenous administration of (25mg/kg) DECAF caused a significant increase in gastric acid secretion. The administration of cimetidine and atropine significantly reduced gastric acid secretion. In conclusion, aqueous extract of Cola nitida and decaffeinated kolanut extract exert significant gastric acid secretion in this study. Also, the mechanisms exhibited by kolanut in stimulating gastric acid secretion in this study could be attributed to stimulating both the histaminergic H2 and cholinergic (Muscarinic M3) receptors since cimetidine and atropine blocked/reduced its effect. This research work was self-funded. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Protective Effect of Olive Leaves Extract in Male Rats after the Administration of Cimetidine

Protective Effect of Olive Leaves Extract in Male Rats after the Administration of Cimetidine

Gastro-protective Effects of Honey in Male Wistar Rats

Honey is consumed as food and also used in the treatments of ailment. However, honey of various types exhibit varying properties. Their therapeutic effects are determined by whether the honey is multifloral or monofloral, and also on the variety of nectars the honey is derived from. Manuka and Tualang types of honey were observed to possess anti-ulcer effects. However, no such report is available for University of Ilorin honey. This study therefore aimed to determine the gastroprotective effects of University of Ilorin honey in Wistar rats using two laboratory models for inducing ulcer (HCl/Ethanol and Indomethacin). Twenty rats each were assigned to four groups for each model of ulcer. The rats were treated for 12 days with the administration of distilled water (control), cimetidine (100 mg/kg b.w.) and University of Ilorin honey (250 mg/kg b.w. in one group and 1000 mg/kg b.w in another group). The rats were fasted for 24 hours after the last treatment. Then, the ulcerogens were given orally. After four hours, the rats were sacrificed, gastric juice was collected and the stomachs were examined for ulceration. The results revealed that pre-treatment with University of Ilorin honey reduced gastric index from 6.80±0.20 (1000 mg/kg b.w. to 2.40±0.24 (control) P&lt;0.05 and 7.20±0.37 (1000 mg/kg b.w.) to 3.20±0.37 (control) P&lt;0.05 in HCl/Ethanol and indomethacin induced ulcer models respectively. There was no significant difference in ulcer index between the cimetidine administered rats and the honey administered group (1000 mg/kg bw.), but the honey group (250 mg/kg bw.) was less effective than the cimetidine group in the models used. Also, there were no changes in gastric acidity in all the groups compared with the control group. In conclusion, the results showed that University of Ilorin honey has protective effect on the gastrointestinal tract which is not due to alteration of gastric acidity.

Associative administration of cimetidine and exogenous melatonin on the endometrial receptors of estrogen, collagen and hormone levels in adult rats

&lt;p&gt;Cloridrato de cimetidina, um bloqueador de receptores H2 das células parietais gástricas, que age reduzindo a secreção de ácido no estômago e tem sido estudado como substância xenoestrogênica. O uso crônico da cimetidina produz distúrbios homonais e toxidade no aparelho reprodutor masculino, além de reduzir o estradiol 2-hidroxilado e aumentar níveis séricos de estradiol e prolactina em mulheres, levando a hiperprolactinemia, que pode ser fator de risco para o câncer. A melatonina, neurohormônio sintetizado pela glândula pineal tem importante papel na função reprodutiva, regulando a produção de estrógeno, progesterrona e prolactina. O estudo testou a hipótese de que a melatonina pode bloquear ou reduzir os efeitos estrogênicos da cimetidina no estroma uterino, interferindo nos receptores de estrógeno, no teor de fibras colágenas e nos níveis hormonais em ratas adultas. Quarenta e cinco (45) ratas albinas divididas em três grupos: I – tratadas com placebo (controle); II – tratado com cimetidina (50 mg/kg) e III – tratado com cimetidina (50 mg/kg) associada à melatonina (200 μg/100 g). Os experimentos foram conduzidos por 7, 14 e 19 dias. Nos grupos tratados apenas com cimetidina, observou-se marcações mais intensas dos receptores REα, maior distribuição das fibras colágenas no endométrio, elevação dos níveis séricos de estrogênio, prolactina e redução da progesterona, nos animais tratados por 19 dias. Na associação cimetidina e melatonina, acredita-se que a melatonina bloqueou esses efeitos. A melatonina tem atividade citoprotetora para efeitos crônicos da cimetidina no estroma endometrial, por reduzir ou prevenir o aumento da síntese de fibras de colágeno pelos fibroblastos regulando a atividade do estrogênio sérico, bem como a expressão de seus receptores endometriais, além de manter os níveis normais de progesterona e prolactina.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;&lt;/strong&gt;&lt;strong&gt;Palavras chave&lt;/strong&gt;: Melatonina, receptor de estrógeno, xenoestrógeno, morfometria, níveis hormonais.&lt;/p&gt;

The PENGARUH PEMBERIAN SIMETIDIN TERHADAP PROFIL FARMAKOKINETIKA PARASETAMOL DENGAN METODE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) TAHUN 2020

Paracetamol is a safe analgesic and antipyretic drug with low side effects, effective and well tolerated. In some cases there is a drug interaction between paracetamol and other drugs. The purpose of this study is to determine the effect of cimetidine administration on paracetamol pharmacokinetic profiles. The method used in this study was an experimental method using 3 rabbits. Rabbits are divided into 3 groups. The first treatment group was given paracetamol suspension, the second treatment group was giving cimetidine 1 hour before paracetamol and the third group was giving cimetidine and paracetamol simultaneously. The dose of the drug has been adjusted to each rabbit. Measurement of plasma paracetamol drug levels was carried out using a High Performance Liquid Chromatography (HPLC) tool. The results of the study showed that the pharmacokinetic parameter values ​​did not show any significant effect on each group. Cimetidine administration simultaneously affects paracetamol pharmacokinetic parameters but not significantly. Likewise with the administration with a time span of 1 hour, did not show any significant changes in the pharmacokinetics of paracetamol.

Carisoprodol pharmacokinetics and distribution in the nucleus accumbens correlates with behavioral effects in rats independent from its metabolism to meprobamate

Carisoprodol (Soma®) is a centrally-acting skeletal-muscle relaxant frequently prescribed for treatment of acute musculoskeletal conditions. Carisoprodol's mechanism of action is unclear and is often ascribed to that of its active metabolite, meprobamate. The purpose of this study was to ascertain whether carisoprodol directly produces behavioral effects, or whether metabolism to meprobamate via cytochrome P450 (CYP450) enzymatic reaction is necessary. Rats were trained to discriminate carisoprodol (100 mg/kg) to assess time course and whether a CYP450 inhibitor (cimetidine) administered for 4 days would alter the discriminative effects of carisoprodol. Additionally, pharmacokinetics of carisoprodol and meprobamate with and without co-administration of cimetidine were assessed via in vivo microdialysis combined with liquid-chromatography–tandem mass spectrometry from blood and nucleus accumbens (NAc). The time course of the discriminative-stimulus effects of carisoprodol closely matched the time course of the levels of carisoprodol in blood and NAc, but did not match the time course of meprobamate. Administration of cimetidine increased levels of carisoprodol and decreased levels of meprobamate consistent with its interfering with metabolism of carisoprodol to meprobamate. However, cimetidine failed to alter the discriminative-stimulus effects of carisoprodol. Carisoprodol penetrated into brain tissue and directly produced behavioral effects without being metabolized to meprobamate. These findings indicate that understanding the mechanism of action of carisoprodol independently of meprobamate will be necessary to determine the validity of its clinical uses.

Impact of the organic cation transporter 2 inhibitor cimetidine on the single-dose pharmacokinetics of the glucosylceramide synthase inhibitor lucerastat in healthy subjects.

Lucerastat is an orally available glucosylceramide synthase inhibitor with a potential to provide substrate reduction therapy for Fabry patients independent of their α-galactosidase A genotype. In humans, lucerastat is mainly eliminated as unchanged parent compound through renal excretion both by active secretion and passive filtration. In vitro studies indicated that lucerastat is a substrate of human organic cation transporter 2 (OCT2) mainly expressed in the kidney. Therefore, this clinical study, conducted in 14 healthy male subjects, investigated the effect of 800 mg twice-daily oral administration of the OCT2 inhibitor cimetidine at steady state on the single-dose pharmacokinetics (PK) of 500 mg lucerastat. The safety and tolerability of lucerastat administered alone and concomitantly with cimetidine were also evaluated. Exposure to lucerastat was slightly higher upon co-administration of cimetidine indicated by geometric mean area under the plasma concentration-time curve from zero to infinity (AUC0-∞) ratio of 1.22 (90% confidence interval [CI] 1.16-1.28). Cimetidine delayed the time to reach maximum lucerastat concentrations (tmax) by 1 h but did not affect its elimination half-life (t½) or maximum plasma concentration (Cmax) as geometric mean ratios were 1.00 (0.91-1.10) and 1.04 (0.92-1.17), respectively, at cimetidine steady state. Lucerastat was safe and well tolerated when given alone and in combination with cimetidine. These results indicate that the single-dose PK of lucerastat are not changed to a clinically relevant extent by cimetidine-mediated OCT2 inhibition, allowing the concomitant use of OCT2 inhibitors with lucerastat without any need for dose adjustment. EudraCT: 2017-003725-14; ClinicalTrials.gov: NCT03380455.

Curcuma longa normalized cimetidine-induced pituitary-testicular dysfunction: Relevance in nutraceutical therapy.

BackgroundThe increasing incidence of chemically induced infertility is both a social threat and a threat to the continuation of life itself. Treatment or management therapy is often expensive. This study investigated the effects of acetone extract of a local plant (Curcuma longa) in a Wistar rat model of cimetidine‐induced pituitary‐testicular dysfunction.MethodsThirty‐five male Wistar rats were divided into 7 groups of 5 rats. After a phytochemical screening of an acetone extract of C. Longa, cimetidine and the extract at three doses, 200, 400 and 600 mg/kg, were orally co‐administered to the rats for 28 consecutive days. Comparisons were made (at P < 0.05) against a control (2 mL/kg distilled water), a standard treatment group (cimetidine + 50 mg/kg vitamin C), a toxic group (60 mg/kg cimetidine) and a group receiving extract alone.ResultsCimetidine administration was associated with deleterious alterations to sperm motility, sperm count and sperm viability, as well as derangements in the plasma levels of FSH, LH and testosterone (P < 0.05). Both brain and testicular GSH and TBARS levels were significantly altered following cimetidine administration, and distortions were seen in the pituitary and testicular histoarchitecture. These changes were significantly normalized by co‐administration of graded doses of the extract, with an associated improvement of both pituitary and testicular histology.ConclusionAcetone extract of C. Longa normalized cimetidine‐induced pituitary‐testicular dysfunction in Wistar rats. This presents the extract as a potential nutraceutical choice against chemically induced reproductive toxicity.

Creatinine clearance after cimetidine administration in a new short procedure: comparison with plasma and renal clearances of iohexol.

BackgroundCreatinine clearance after cimetidine administration (Cim-CreatClr) was once proposed as a method of glomerular filtration rate (GFR) measurement, but has been largely abandoned. We investigated whether a new short procedure for Cim-CreatClr determination could be considered an appropriate method for GFR measurement.MethodsA 150-min protocol involving oral cimetidine administration was developed to determine Cim-CreatClr. In total, 168 patients underwent simultaneous assessments of creatinine clearance before and after cimetidine administration [basal creatinine clearance (Basal-CreatClr) and Cim-CreatClr, respectively], renal iohexol clearance and plasma iohexol clearance (R-iohexClr and P-iohexClr, respectively). We compared the agreement between the various methods of GFR measurement, using Bland–Altman plots to determine biases, precisions (standard deviation of the biases) and accuracy (proportions of GFR values falling within 10, 15 and 30% of the mean: P10, P15 and P30, respectively).ResultsAfter cimetidine administration, Basal-CreatClr decreased by 19.8% [95% reference limits of agreement (95% LoA): −2.2 to 41.7%]. The bias between Cim-CreatClr and P-iohexClr was −0.6% (95% LoA −26.8 to 28%); the precision was 14.0%; P10, P15 and P30 were 57.1% [95% confidence interval (95% CI) 49.3 to 64.7%], 73.2% (95% CI 65.8 to 79.7%) and 97.0% (95% CI 93.2 to 99.0%), respectively. Due to the positive bias (16.7%; 95% LoA −3.6 to 36.9%) of Cim-CreatClr relative to R-iohexClr, accuracy of Cim-CreatClr relative to R-iohexClr was poor despite a good precision (10.3%).ConclusionsOur study shows a high level of agreement between Cim-CreatClr and P-iohexClr. These results suggest that this short Cim-CreatClr procedure is a valid method for GFR measurement, which might be useful, in particular, in situations in which P-iohexClr is not suitable or not available.

Increased Glomerular Filtration Rate in Early Stage of Balkan Endemic Nephropathy.

Background: A previous study indicated that Balkan endemic nephropathy (BEN) patients in the early stage of the disease had significantly higher creatinine clearance (Ccr) than healthy persons. The aim of the study was to assess whether tubular creatinine secretion affects Ccr in early stages of BEN and to check the applicability of serum creatinine-based glomerular filtration rate (GFR) equations in these patients. Methods: The study involved 21 BEN patients with estimated GFR (eGFR) above 60 mL/min/1.73 m2, excluding any conditions that could affect GFR or tubular creatinine secretion, and 15 healthy controls. In all participants Ccr with and without cimetidine and iohexol clearance (mGFR) were measured and eGFR calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease Study (MDRD) equations. Glomerular hyperfiltration cutoff (GFR-HF) was calculated. Results: There was no significant difference between the groups in Ccr before and after cimetidine or for eGFR, but mGFR was significantly higher in BEN patients than in controls (122.02 ± 28.03 mL/min/1.73 m2 vs. 101.15 ± 27.32 mL/min/1.73 m2; p = 0.032). Cimetidine administration reduced Ccr by 10% in both groups. The ratio of Ccr to mGFR was significantly above one in seven BEN patients and five controls and their mGFR values were similar. Seven other patients and eight controls had this ratio equal to one, while values below one were recorded for seven more patients and two controls. mGFR of all these 14 patients was significantly higher than that of healthy controls (129.88 ± 27.52 mL/min/1.73 m2 vs. 107.43 ± 19.51 mL/min/1.73 m2; p = 0.009). Mean GFR-HF was significantly higher than mGFR in controls, but these two values were similar in BEN patients. eGFR underestimated mGFR in both BEN patients and controls. Conclusion: The ratio of Ccr to mGFR and mGFR to GFR-HF indicated that elevated mGFR in early stages of BEN could be explained by increased glomerular filtration, but tubular creatinine secretion augmented Ccr in a smaller proportion of patients, who did not differ from healthy subjects.

Rhinitis following intraoperative gastro-oesophageal reflux in a dog

A four-month-old, male dog underwent surgical repair of femoral and pelvic fracture. The dog was premedicated with acepromazine combined with morphine; anaesthesia was induced with propofol to effect and maintained...

Metformin targets brown adipose tissue in vivo and reduces oxygen consumption in vitro.

To test the hypothesis that brown adipose tissue (BAT) is a metformin target tissue by investigating in vivo uptake of [11 C]-metformin tracer in mice and studying in vitro effects of metformin on cultured human brown adipocytes. Tissue-specific uptake of metformin was assessed in mice by PET/CT imaging after injection of [11 C]-metformin. Human brown adipose tissue was obtained from elective neck surgery and metformin transporter expression levels in human and murine BAT were determined by qPCR. Oxygen consumption in metformin-treated human brown adipocyte cell models was assessed by Seahorse XF technology. Injected [11 C]-metformin showed avid uptake in the murine interscapular BAT depot. Metformin exposure in BAT was similar to hepatic exposure. Non-specific inhibition of the organic cation transporter (OCT) protein by cimetidine administration eliminated BAT exposure to metformin, demonstrating OCT-mediated uptake. Gene expression profiles of OCTs in BAT revealed ample OCT3 expression in both human and mouse BAT. Incubation of a human brown adipocyte cell models with metformin reduced cellular oxygen consumption in a dose-dependent manner. These results support BAT as a putative metformin target.

Gastroprotective and Ulcer Healing Effects of Camel Milk and Urine in HCl/EtOH, Non-steroidal Anti-inflammatory Drugs (Indomethacin), and Water-Restraint Stress-induced Ulcer in Rats.

Background:Camel milk has been reportedly used to treat dropsy, jaundice, tuberculosis, and diabetes while camel urine is used to treat diarrhea and cancer. However, there is no scientific evidence on the antiulcer activity of camel milk and urine. Thus, the present is designed to investigate the gastroprotective and ulcer healing effect of camel milk and urine on experimentally induced gastric ulcer models in rats.Materials and Methods:The gastroprotective effect was investigated in HCl/EtOH, water-restraint stress (WRS) and non-steroidal anti-inflammatory drugs (indomethacin)-induced ulcer models while ulcer healing activity was investigated in indomethacin-induced ulcer model. Cimetidine (100 mg/kg) was used as a standard antiulcer drug.Results:Acute toxicity study done up to a dosage of 10 ml/kg of camel milk and urine showed no signs of toxicity and mortality among the rats, indicating the present dosage of 5 ml/kg is safe to be administered to the rats. In the HCl/EtOH model, oral administration of cimetidine (100 mg/kg), camel urine (5 ml/kg), and camel milk (5 ml/kg) significantly (P < 0.05) inhibited gastric lesions by 83.7, 60.5 and 100%, respectively. In the WRS-induced model, cimetidine, and camel urine showed an ulcer inhibition of 100% while camel milk showed an inhibition of 50%. Similarly, in the indomethacin-induced ulcer model, cimetidine, camel milk, and urine showed an ulcer inhibition of 100, 33.3, and 66.7%, respectively. In addition, camel milk and urine also showed a significant (P < 0.05) ulcer healing effect of 100% in indomethacin-induced ulcer model, with no ulcers observed as compared to that of cimetidine, which offers a healing effect of 60.5%.Conclusion:The antiulcer activity of camel milk and urine may be attributed to its cytoprotective mechanism and antioxidant properties.SUMMARY Acute toxicity findings revealed the dosage of 10 ml/kg of camel milk and urine seems no toxic and indicating the dosage of 5 ml/kg is safe to be administered to the ratsOral administration of cimetidine (100 mg/kg), camel urine (5 ml/kg), and camel milk (5 ml/kg) significantly inhibited gastric lesions by 83.7, 60.5 and 100% in the HCl/EtOH experimental modelThe results of this investigation have proven that camel milk and urine showed strong ulcer healing effect in indomethacin-induced gastric damage. Abbreviations used: NSAIDs: Non-steroidal anti-inflammatory drugs, UI: Ulcer index, ANOVA: One-way analysis of variance, WRS: Water-restraint stress, ROS: Reactive oxygen species

The influence of oral cimetidine administration on creatinine clearance in chilren with chronic renal failure: A preliminary study

Background Serum creatinine and creatinine clearance are usedto assess glomerular filtration rate but have a major disadvantagesince a variable amount of creatinine is secreted in the proximaltubule. This may cause an unpredictable overestimation of GFR.Tubular creatinine secretion can be blocked by cimetidine throughcompetitive inhibition of cation transport in the proximal tubularluminal membrane.Objective Cimetidine administration might improve the reliabilityof creatinine as a marker of glomerular filtration.Methods A preliminary study with a one-group pretest-posttestdesign in 11 children with chronic renal failure. Serum cystatin Clevel as reference value was compared with creatinine clearancemeasured before and after oral ingestion of cimetidine. The doseof cimetidine was adjusted with the GFR using Schwartz formula.Statistical evaluation was done with the Wilcoxon signed rankstest.Result The mean creatinine clearance before cimetidine adminis-tration was 27.4 (SD 14.6) ml/minute/1.73 m 2 BSA, and decreasedafter cimetidine to 21.1 (SD 13,1) ml/minute/1.73 m 2 BSA (p=0.015).Conclusion Oral cimetidine was effective in inhibiting creatininetubular secretion. This study could not prove that cimetidine im-proves the accuracy of creatinine clearance

The effects of cimetidine chronic treatment on conventional antiepileptic drugs in mice

The aim of this study was to evaluate the effects of 1-day, 7-day and 14-day administrations of cimetidine on the anticonvulsant activity of conventional antiepileptic drugs (AEDs; valproate, carbamazepine, phenytoin and phenobarbital) against maximal electroshock (MES)-induced convulsions in mice. Electroconvulsions were evoked in Albino Swiss mice by a current delivered via ear-clip electrodes. In addition, the effects of cimetidine, AEDs alone and their combinations were studied on performance and long-term memory tests. Pharmacokinetic changes in plasma and brain concentrations of AEDs after cimetidine administration were evaluated with immunofluorescence. Cimetidine (up to 100mg/kg) after 1-day administration did not affect the electroconvulsive threshold in animals. Moreover, in the 14-day treatment, cimetidine administered at a dose of 40mg/kg did not significantly change the electroconvulsive threshold in the MES-test, cimetidine administered 14-day (at 20mg/kg) significantly increased the anticonvulsant activity of carbamazepine, staying without effects after a 1-day and 7-day studies. In contrast, both the 7-day and 14-day administrations of cimetidine resulted in significant reductions of protective efficacy of the phenobarbital. Only valproate and phenytoin were not affected by cimetidine (20mg/kg) in all experimental period. Cimetidine administered 1-day, did not alter total brain concentrations and free plasma levels of all AEDs tested, whilst the 14-day study elevated carbamazepine plasma and brain concentration and reduced phenobarbital brain concentration. Cimetidine co-applied with AEDs did not impair performance of mice evaluated in the chimney test however, it worsened long-term memory in animals. Based on this preclinical study, a special caution is advised when treating epileptic patients with combinations of phenobarbital or carbamazepine with cimetidine.

Repurposing drugs in oncology (ReDO)-cimetidine as an anti-cancer agent.

Cimetidine, the first H2 receptor antagonist in widespread clinical use, has anti-cancer properties that have been elucidated in a broad range of pre-clinical and clinical studies for a number of different cancer types. These data are summarised and discussed in relation to a number of distinct mechanisms of action. Based on the evidence presented, it is proposed that cimetidine would synergise with a range of other drugs, including existing chemotherapeutics, and that further exploration of the potential of cimetidine as an anti-cancer therapeutic is warranted. Furthermore, there is compelling evidence that cimetidine administration during the peri-operative period may provide a survival benefit in some cancers. A number of possible combinations with other drugs are discussed in the supplementary material accompanying this paper.

Cimetidine administration decreases radiogenic damage on the thyroid gland in mice

Purpose: To study if Cimetidine administration could ameliorate the thyroid damage in external radiation.Materials and methods: Forty healthy male adult mice were used in the present study. The animals were randomized into four groups. Untreated mice (Group 1) that received 1 mg/kg saline intraperitoneally (IP). Group 2 received a single 10 Gy gamma radiation dose with 1 mg/kg saline IP and group 3 were treated with Cimetidine IP. Group 4 was irradiated 1 hour after treatment with Cimetidine. The serum were assayed for the contents of triiodothyronine (T3), tetraiodothyronine (T4), thyroid stimulating hormone (TSH), Free T4 (FT4) and Cortisol using a radioimmunological technique 7 days following radiation. The thyroid tissue was processed and stained with hematoxylin and eosin (H&E), and periodic acid-Schiff (PAS) for histological examination. Data were statistically analyzed using Tukey's post-hoc test and were considered significant at p < 0.05.Results: External radiation resulted in weight loss and reduction of serum thyroid hormone levels. However, Cimetidine administration prevented marked changes. Histological study showed that Cimetidine injection to irradiated mice minimized the thyroid damage.Conclusions: These findings suggested that Cimetidine administration 1 hour before radiation exposure was potent in ameliorating the thyroid damages.