In-vivo anti-inflammatory and anti-pyretic activities of Manilkara zapota leaves in albino Wistar rats

Objective

To screen ethanolic extracts of Manilkara zapota leaves (Family: Sapotaceae) and its different solvent soluble fractions for possible anti-inflammatory, anti-pyretic activities in experimental albino Wistar rats.

Methods

Anti-inflammatory activity was evaluated by carrageenan induced paw edema method; anti-pyretic potential was determined by yeast-induced pyrexia method in albino Wistar rats.

Results

In evaluation of anti-inflammatory activity the crude ethanolic (300 mg/kg) and ethyl acetate extract (300 mg/kg) showed significant inhibition of paw edema by 91.98% and 92.41% (P<0.001) respectively at 4th h compared to standard diclofenac (86.08% inhibition). In anti-pyretic study by yeast-induced pyrexia in albino Wistar rats, the ethanol extract (300 mg/kg) reduced temperature from 37.90 °C to 37.41 °C (P<0.01) and 37.07 °C (P<0.001) in 3rd and 4th h respectively. Similarly, both petroleum ether and ethyl acetate fractions exhibited significant anti-pyretic property (P<0.001). The maximum body temperature lowering effect (36.86 °C) was noticed by petroleum ether fraction.

Conclusions

The findings of the studies demonstrated both anti-inflammatory and anti-pyretic activities of the leaves of Manilkara zapota which could be the therapeutic option against inflammatory disease and pyrexia.     

The Effects of Broccoli Sprout Extract Containing Sulforaphane on Lipid Peroxidation and Helicobacter pylori Infection in the Gastric Mucosa

Background/Aims

The aims of this study were to investigate whether a broccoli sprout extract containing sulforaphane (BSES) inhibited the Helicobacter pylori infection density and exerted an antioxidative effect on gastric mucosal damage.

Methods

The enrolled subjects were randomized in a double-blinded manner into three groups. Finally, 33 H. pylori (+) BSES treatment subjects (group A), 28 H. pylori (+) placebo subjects (group B), and 28 H. pylori (−) BSES treatment subjects (group C) were studied. H. pylori infection density was indirectly quantified by a ¹³C-urea breath test (UBT), and the ammonia concentration in gastric juice aspirates was measured through gastroscopic examination. Malondialdehyde (MDA), an oxidative damage biomarker, and reduced glutathione (GSH), an antioxidant biomarker, were measured in the gastric mucosa by an enzyme-linked immunosorbent assay.

Results

BSES treatment did not significantly affect the UBT values or ammonia concentration in group A (p=0.634 and p=0.505, respectively). BSES treatment did significantly reduce mucosal MDA concentrations in group A (p<0.05) and group C (p<0.001), whereas the gastric mucosal GSH concentrations did not differ before and after treatment in any of the groups.

Conclusions

BSES did not inhibit the H. pylori infection density. However, BSES prevented lipid peroxidation in the gastric mucosa and may play a cytoprotective role in H. pylori-induced gastritis.     

Phytochemical screening and antioxidant capacity of the aerial parts of Thymelaea hirsuta L.

Objective

To assess antioxidant activities of different aerial parts of Thymelaea hirsuta (T. hirsuta) from west Algeria, and to search for new sources of safe and inexpensive antioxidants.

Methods

Samples of leaves, stems and flowers from T. hirsuta were tested for total phenolic content, flavonoids content, and evaluation its total antioxidant activity, were done using the spectrophotometric analyses.

Results

Results of preliminary phytochemical screening of leaf, flower and stem of T. hirsuta revealed the presence of tannins, alkaloids, steroids, saponins, coumarins, reducteurs compound and anthraquinones. The total phenolics and flavonoids were estimated. The aqueous extracts of the aerial parts of T. hirsuta showed potent in vitro antioxydant activities using various models viz, DPPH scavenging assay, ferric reducing antioxidant power (FRAP) and ABTS radical scavenging activity.

Conclusions

On the basis of the results obtained, T. hirsuta extracts are rich sources of natural antioxidants appears to be an alternative to synthetic antioxidants and this justifies its therapeutic usage.     

Effects of hydro-ethanol extract of Citrullus colocynthis on blood glucose levels and pathology of organs in alloxan-induced diabetic rats

Objective

To evaluated the differential effects of ethanol extraction of Citrullus colocynthis (C. colocynthis) on the blood glucose concentration and pathology of pancreas, liver, lungs, kidney and gastrointestinal tract in the alloxan induced diabetes in rats.

Methods

Diabetes mellitus was induced in 20 adult female Albino rats, using intraperitoneal injection of 120 mg/kg alloxan. The diabetic rats were randomly assigned into two equal groups. The first group was treated with the extract of C. colocynthis seed (300 mg/kg) and the rats of the second group, as an untreated diabetic group, received ordinary diet. Ten non diabetic rats remained as a normal control group.

Results

The results of this study indicate that C. colocynthis was able to reduce blood glucose significantly compared with the control diabetic group (P<0.05). Histopathologically, alloxan resulted in severe necrotic changes in the pancreatic islets, especially in the central area of the islets. Tissue sections of the pancreas in the treated rats demonstrated enhanced regeneration of B cells and increased size of pancreatic islets. Liver of the treated diabetic rats revealed significant improvement of the hepatic tissue compared to those of the untreated diabetic rats.

Conclusions

The present study indicated a significant anti-hyperglycemic effect of C. colocynthis seed and supported its traditional usage in treatment of diabetes mellitus.     

Antidiabetic activity of aqueous leaf extract of Atriplex halimus L. (Chenopodiaceae) in streptozotocin-induced diabetic rats

Objective

To investigate the antidiabetic effect of A. halimus leaf in streptozotocin-induced diabetic rats.

Methods

The aqueous extract of the plant leaf was tested for its efficacy in streptozotocin-induced diabetic rats. The extract was evaluated for its acute and short term general toxicity in male mice and for its antihyperglycemic activity using glucose tolerance test in rats. The aqueous extract was subjected to phytochemical screening and determination of total phenolic contents.

Results

The statistical data indicated the significant increase in the body weight and decrease in the blood glucose and hepatic levels. The total protein level was significantly increased when treated with the extract.

Conclusions

These results suggest that the aqueous leaf extract of A. halimus has beneficial effects in reducing the elevated blood glucose level and hepatic levels in streptozotocin-induced diabetic rats.     

Evaluation of antioxidant potential of leaves of Leonotis nepetifolia and its inhibitory effect on MCF7 and Hep2 cancer cell lines

Objective

To investigate the antioxidant and antiproliferative potential of Leonotis nepetifolia (L. nepetifolia) leaves.

Methods

The leaves of L. nepetifolia were subjected to extraction using three different solvents and the antioxidant potential of those extracts were tested by using various in vitro assays. Further, the best screened extract was analyzed for its phytochemical profile by both qualitative and quantitative assays. In order to determine its anti-proliferative activity, the best screened extract was treated with breast and laryngeal cancer cell lines such as MCF-7 cells and Hep2 cells, respectively. The cytotoxicity of the extract was also studied using MTT assay. The inhibitory effect of the extract of leaves of L. nepetifolia on the selected cell-line DNA was determined by DNA fragmentation assay. Also, the extract was subjected to TLC and bioautography analysis.

Results

The DPPH assay showed methanol extract of L. nepetifolia leaves to be more significant in scavenging free radicals with inhibition percentage of 60.57%. From the data obtained, the methanol extract proved to be significant in all anti-oxidant assays and this effect was well comparable with the standard used in the study. The predominant phytochemicals such as phenols and flavonoids were further quantified as 0.107% and 0.089%. The cytotoxicity assay showed that the cell viability increased with increasing concentration of methanol extract. In addition, the extract caused dose dependent damage to the cancer cell lines MCF-7 and Hep2.

Conclusions

Our study suggests that the leaves of L. nepetifolia were significant in scavenging free radicals and causing damage to proliferative cells. Further mechanistic studies would help in proving the efficiency of the selected plant under in vivo conditions.     

The effect of Ligustrum delavayanum on isolated perfused rat heart

BACKGROUND:

Extract of ligustrum leaves (Ligustrum delavayanum Hariot [Oleaceae]) is well known in traditional Chinese medicine. One of the active components, oleuropein, displays vasodilating and hypotensive effects.

OBJECTIVE:

To analyze the effect of 0.008% lyophilized extract of ligustrum dissolved in 0.5% ethanol on heart function.

ANIMALS AND METHODS:

Experiments were done on isolated rat hearts perfused by the Langendorff method in control conditions and during ischemic-reperfusion injury.

RESULTS:

Application of ligustrum induced positive inotropic and vasodilating effects in spontaneously beating hearts. Pretreatment of the hearts with ligustrum reduced left ventricular diastolic pressure measured during reperfusion and improved left ventricular contraction compared with hearts without any pretreatment. Ligustrum significantly suppressed the incidence and duration of cardiac reperfusion arrhythmias, expressed as G-score, from 7.40±0.58 in nontreated rats to 1.97±0.50.

DISCUSSION:

Application of ligustrum or ethanol alone induced changes in coordination between atria and ventricles during ischemia-reperfusion injury. The ‘g-score’, a new parameter summing the incidence and duration of atrioventricular blocks, atrioventricular dissociation and cardiac arrest, is introduced. The g-scores with ligustrum pretreatment were higher during ischemia than during reperfusion. Ethanol significantly depressed myocardial contractility and coronary flow, and nonsignificantly decreased heart rate of isolated rat hearts. Electrical changes observed during coronary reperfusion in the presence of ethanol were accompanied by deterioration of contractile function.

CONCLUSIONS:

Ligustrum had a significant protective effect on rat myocardium against ischemic-reperfusion injury. Ethanol partially attenuated the protective effect of ligustrum.     

Protective effects of Lactuca sativa ethanolic extract on carbon tetrachloride induced oxidative damage in rats

Objective

To study the protective effects of the ethanolic extract of lettuce (Lactuca sativa L. var. longifolia) leaves against the toxicity caused by carbon tetrachloride (CCl₄) in reproductive system of rats.

Methods

Lettuce leaves were dried and extracted with ethanol (plant: solvent, 1:10, w/v). The extract was filtered and evaporated to yield dried lettuce extract. Animals were divided into seven groups and treated with CCl₄ and different concentrations of lettuce extract. At the end of the experimental period, the animals were sacrificed and blood was collected and centrifuged for serum separation. Body weights, testis size, histopathology of testis and liver, catalase (CAT) activity, superoxide dismutase (SOD) activity, peroxidase (POD) activity, reduced glutathione (GSH), glutathione peroxidase activity (GSH-Px), thiobarbituric acid reactive substances (TBARS), nitrite level, and serum hormones were determined.

Results

Oxidative stress induced by CCl₄ (2 mL/kg body weight) in rat decreases the increase in body weight and relative testis weight. It also markedly increases the level of TBARS and nitrites along with corresponding decrease in reduced glutathione and various antioxidant enzymes in testis (i.e., CAT, POD, SOD and GSH-Px). Serum level of testosterone, luteinizing hormone and follicle stimulating hormone was decreased while estradiol and prolactin were increased during CCl₄ treatment. Histopathology of CCl₄-treated rats indicated the partial degeneration of germ and leydig cells along with deformities in spermatogenesis. Supplementation of lettuce extract (100, 150, 200 mg/kg body weight orally) once a week for 10 weeks results in decrease of TBARS and nitrite, while increase in antioxidant enzymes; CAT, POD, SOD, GSH-Px and GSH contents. Serum level of testosterone, luteinizing hormone, follicle stimulating hormone, estradiol, prolactin, histology, body weight and relative testis weight was also concomitantly restored to near normal level by lettuce extract supplementation to CCl₄-intoxicated rat.

Conclusions

The results clearly demonstrate that lettuce extract treatment augments the antioxidants defense mechanism against CCl₄-induced toxicity and provides evidence that it may have a therapeutic role in free radical mediated diseases.     

The Impact of IFNL4 rs12979860 Polymorphism on Spontaneous Clearance of Hepatitis C; A Case-Control Study

Background:

About 30% of individuals with hepatitis C virus (HCV) infection are able to clear HCV spontaneously. Differences in host genetics affect the outcome of HCV infection. Single nucleotide polymorphisms (SNPs) of the Interferon lambda (IFNL) genes were associated with spontaneous and treatment-induced clearance of HCV infection.

Objectives:

The aim of this study was to evaluate the association between the IFNL4 rs12979860 SNP and spontaneous clearance of HCV infection in Iranian population.

Materials and Methods:

A case-control study was designed on 91 cases with spontaneous HCV infection clearance and 259 patients with persistent HCV infection as the control group. The rs12979860 SNP was assessed as the most common IFNL polymorphism by PCR-RFLP method.

Results:

Distribution of rs12979860 CC genotype in the spontaneous clearance group was around two folds of its distribution in chronic hepatitis C group (P < 0.001, OR = 4.09, 95% CI = 2.44-6.86).

Conclusions:

The rs12979860 SNP was observed as a strong host genetic factor associated with spontaneous clearance of hepatitis C infection.     

Assessment of In vivo antioxidant properties of Dacryodes edulis and Ficus exasperata as anti-malaria plants

Objective

To evaluate the phytochemical profile and potential anti-oxidant properties of Dacryodes edulis and Ficus exasperata.

Methods

Six groups of Albino rats were intoxicated with tetrachloromethane (CCl₄) for 2 d, prior to 7 d administration of 50 mg/kg, 100 mg/kg, 200 mg/kg ethanol extracts of plants and three control remidies which is Tween 80 (placebo), CCl₄ (negative control) and vitamin E (positive control). Tissue homogenates were employed in assessing the thiobarbituric acid reactive substances expressed as malondialdehyde (MDA) levels, reduced glutathione (GSH) and catalase (CAT) activities.

Results

Phytochemical profiling of the plants showed the presence of reducing sugars, flavonoids, saponins and tannins, except alkaloids and terpenoids in F. exasperata and cardiac glycosides in D. edulis. Generally, significantly different values (P<0.05) were recorded for blood than for liver homogenates. Elevated MDA levels were observed for the CCl₄ treated group (negative control). However, lower MDA levels comparable to vitamin E (positive control) were recorded for all D. edulis and the 200 mg/kg F. exasperata pre-treatments. CAT levels were significantly (P<0.05) raised in the 100 mg/kg and 200 mg/kg pretreatments for blood and the 200 mg/kg pretreatments for liver, than for Vit E. CCl₄ reduced GSH levels were reversed significantly (P<0.05) in blood by D. edulis and by the 100 mg/kg and 200 mg/kg F. exasperata pretreatments in blood and liver tissues. The mean dose-dependent analysis shows increasing fall in MDA levels with dosage.

Conclusions

The plant extracts exhibited dose-dependent oxidative stress suppressive action. This may justify their use for the traditional preparation of anti-malarial remedies.     

Plasma choline metabolites associate with metabolic stress among young overweight men in a genotype-specific manner

OBJECTIVES:

We aimed to test the hypotheses that (i) plasma choline metabolites differ between normal (body mass index (BMI)<25 kg m⁻²) and overweight (BMI ⩾25 kg m⁻²) men, and (ii) an elevated BMI alters associations between plasma choline metabolites and indicators of metabolic stress.

DESIGN:

This was a cross-sectional study. A one-time fasting blood sample was obtained for measurements of the choline metabolites and metabolic stress indicators (that is, serum alanine aminotransferase (ALT), glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides and homocysteine), and for genotype determination.

SUBJECTS:

The analysis was conducted with 237 Mexican American men with a median age of 22 years.

RESULTS:

Compared with men with a normal BMI (n=98), those with an elevated BMI (n=139) had 6% lower (P=0.049) plasma betaine and an 11% lower (P=0.002) plasma betaine to choline ratio. Among men with an elevated BMI, plasma betaine and the plasma betaine to choline ratio positively associated (P⩽0.044) with a favorable serum cholesterol profile, and inversely associated (P=0.001) with serum ALT, a marker of liver dysfunction. The phosphatidylethanolamine N-methyltransferase (PEMT) 5465G→A (rs7946) genotype interacted (P⩽0.007) with the plasma betaine to choline ratio to modulate indicators of metabolic stress with stronger inverse associations observed among overweight men with the PEMT 5465GG genotype.

CONCLUSIONS:

Plasma choline metabolites predict metabolic stress among overweight men often in a genotype-specific manner. The diminished betaine among overweight men coupled with the inverse association between betaine and metabolic stress suggest that betaine supplementation may be effective in mitigating some of the metabolic insults arising from lipid overload.     

Clostridium difficile infection worsens the prognosis of ulcerative colitis

BACKGROUND:

The impact of Clostridium difficile infections among ulcerative colitis (UC) patients is well characterized. However, there is little knowledge regarding the association between C difficile infections and postoperative complications among UC patients.

OBJECTIVE:

To determine whether C difficile infection is associated with undergoing an emergent colectomy and experiencing postoperative complications.

METHODS:

The present population-based case-control study identified UC patients admitted to Calgary Health Zone hospitals for a flare between 2000 and 2009. C difficile toxin tests ordered in hospital or 90 days before hospital admission were provided by Calgary Laboratory Services (Calgary, Alberta). Hospital records were reviewed to confirm diagnoses and to extract clinical data. Multivariate logistic regression analyses were performed among individuals tested for C difficile to examine the association between C difficile infection and emergent colectomy and diagnosis of any postoperative complications and, secondarily, an infectious postoperative complication. Estimates were presented as adjusted ORs with 95% CIs.

RESULTS:

C difficile was tested in 278 (58%) UC patients and 6.1% were positive. C difficile infection was associated with an increased risk for emergent colectomy (adjusted OR 3.39 [95% CI 1.02 to 11.23]). Additionally, a preoperative diagnosis of C difficile was significantly associated with the development of postoperative infectious complications (OR 4.76 [95% CI 1.10 to 20.63]).

CONCLUSION:

C difficile diagnosis worsened the prognosis of UC by increasing the risk of colectomy and postoperative infectious complications following colectomy. Future studies are needed to explore whether early detection and aggressive management of C difficile infection will improve UC outcomes.     

WIN OVER study: Efficacy and safety of olmesartan in Indian hypertensive patients: Results of an open label,non-comparative,multi-centric,post marketing observational study

Background

Hypertension is a global health problem. Multiple classes of drugs including angiotensin receptor blockers (ARBs) are available for the treatment of hypertension. Olmesartan is a relatively newer ARB used in hypertension management.

Objective

To assess the efficacy and safety of WIN-BP (Olmesartan 20 mg/40 mg) tablet in Indian patients with hypertension.

Material and methods

An open label, non-comparative, multi-centric, real world post marketing observational study included Indian adult hypertensive patients who were treated with olmesartan 20 mg/40 mg tablet once daily for six months. The primary outcome was reduction of systolic blood pressure (SBP) to <140 mmHg and diastolic BP (DBP) to <90 mmHg at 3 and 6 months after initiation of treatment with olmesartan. All reported adverse events were recorded.

Results

A total of 8940 patients were enrolled in this study. Baseline SBP of 164 mmHg was reduced to 153, 145, 134 and 130 mmHg at the end of 15 days, 1, 3 and 6 months respectively. Similarly, baseline DBP of 100 mmHg was reduced to 93, 89, 84 and 82 mmHg at the end of 15 days, 1, 3 and 6 months respectively. The reduction in both systolic and diastolic blood pressure from day 15 to month 6 was statistically significant (p < 0.0001) with olmesartan treatment. The percentage of responders for both systolic and diastolic blood pressure increased consistently from day 15 to month 6. Only 0.08% patients reported the adverse events. No serious adverse event was reported in the study.

Conclusion

Olmesartan 20 mg/40 mg is effective and well tolerated without any serious adverse events in patients with hypertension.     

Substitutions in Penicillin-Binding Protein 1 in Amoxicillin-Resistant Helicobacter pylori Strains Isolated from Korean Patients

Background/Aims

A worldwide increase in amoxicillin resistance in Helicobacter pylori is having an adverse effect on eradication therapy. In this study, we investigated the mechanism of the amoxicillin resistance of H. pylori in terms of amino acid substitutions in penicillin-binding protein 1 (PBP1).

Methods

In total, 150 H. pylori strains were isolated from 144 patients with chronic gastritis, peptic ulcers, or stomach cancer. The minimum inhibitory concentrations (MICs) of the strains were determined with a serial 2-fold agar dilution method. The resistance breakpoint for amoxicillin was defined as >0.5 µg/mL.

Results

Nine of 150 H. pylori strains showed amoxicillin resistance (6%). The MIC values of the resistant strains ranged from 1 to 4 µg/mL. A PBP1 sequence analysis of the resistant strains revealed multiple amino acid substitutions: Val16→Ile, Val45→Ile, Ser414→Arg, Asn562→Tyr, Thr593→Ala, Gly595→Ser, and Ala599→Thr. The natural transformation of these mutated genes into amoxicillin-sensitive strains was performed in two separate pbp1 gene segments. A moderate increase in the amoxicillin MIC was observed in the segment that contained the penicillin-binding motif of the C-terminal portion, the transpeptidase domain.

Conclusions

pbp1 mutation affects the amoxicillin resistance of H. pylori through the transfer of the penicillin-binding motif.     

Effect of trans fatty acid intake on abdominal and liver fat deposition and blood lipids: a randomized trial in overweight postmenopausal women

Background:

Intake of industrially produced trans fatty acids (TFAs) is, according to observational studies, associated with an increased risk of cardiovascular disease, but the causal mechanisms have not been fully elucidated. Besides inducing dyslipidemia, TFA intake is suspected to promote abdominal and liver fat deposition.

Objective:

We examined the effect of a high intake of TFA as part of an isocaloric diet on whole-body, abdominal and hepatic fat deposition, and blood lipids in postmenopausal women.

Methods:

In a 16-week double-blind parallel intervention study, 52 healthy overweight postmenopausal women were randomized to receive either partially hydrogenated soybean oil providing 15.7 g day⁻¹ of TFA or a control oil with mainly oleic and palmitic acid. Before and after the intervention, body composition was assessed by dual-energy X-ray absorptiometry, abdominal fat by magnetic resonance (MR) imaging, and liver fat by ¹H MR spectroscopy.

Results:

Compared with the control fat, TFA intake decreased plasma high-density lipoprotein (HDL)-cholesterol by 10%, increased low-density lipoprotein (LDL)-cholesterol by 18% and resulted in an increased LDL/HDL-cholesterol ratio (baseline adjusted mean (95% CI) difference between diet groups 0.41 (0.22; 0.60); P<0.001). TFA tended to increase the body fat (0.46 (−0.20; 1.17) kg; P=0.16) and waist circumference (1.1 (−0.1; 2.4) cm; P=0.08) more than the control fat, whereas neither abdominal nor liver fat deposition was affected by TFA.

Conclusion:

The adverse effect of dietary TFA on cardiovascular disease risk involves induction of dyslipidemia, and perhaps body fat, whereas weight gain-independent accumulation of ectopic fat could not be identified as a contributory factor during short-term intake.     

Single nucleotide polymorphism in RECQL and survival in resectable pancreatic adenocarcinoma

Background:

RECQL is a DNA helicase involved in DNA mismatch repair. The RECQL polymorphism, 3′ untranslated region (UTR) A159C, was previously associated with overall survival of patients with resectable pancreatic adenocarcinoma treated with neoadjuvant chemoradiation. In the present study, we examined RECQL for somatic mutations and other polymorphisms and compared these findings with the outcome in patients who received adjuvant or neoadjuvant chemoradiation. We hypothesized that RECQL (i) would be mutated in cancer, (ii) would have polymorphisms linked to the 3′UTR A159C and that either or both events would affect function. We also hypothesized that (iii) these changes would be associated with survival in both cohorts of patients.

Material and methods:

We sequenced RECQL''s 15 exons and surrounding sequences in paired blood and tumour DNA of 39 patients. The 3′UTR A159C genotype was determined in blood DNA samples from 176 patients with resectable pancreatic adenocarcinoma treated with adjuvant (53) or neoadjuvant (123) chemoradiation. Survival was calculated using the Kaplan–Meier method, with log rank comparisons between groups. The relative impact of genotype on time to overall survival was performed using the Cox proportional hazards model.

Results:

Somatic mutations were found in UTRs and intronic regions but not in exonic coding regions of the RECQL gene. Two single nucleotide polymorphisms (SNPs), located in introns 2 and 11, were found to be part of the same haplotype block as the RECQL A159C SNP and showed a similar association with overall survival. No short-term difference in survival between treatment strategies was found. We identified a subgroup of patients responsive to neoadjuvant therapy in which the 159 A allele conferred strikingly improved long-term survival.

Discussion:

The RECQL 3′UTR A159C SNP is not linked with other functional SNPs within RECQL but may function as a site for regulatory molecules. The mechanism of action needs to be clarified further.     

Bucillamine improves hepatic microcirculation and reduces hepatocellular injury after liver warm ischaemia-reperfusion injury

Background:

Liver transplantation and resection surgery involve a period of ischaemia and reperfusion to the liver which initiates an inflammatory cascade resulting in liver and remote organ injury. Bucillamine is a low-molecular-weight thiol antioxidant that is capable of rapidly entering cells.

Methods:

The effect of bucillamine was studied in a rat model of liver ischaemia–reperfusion injury with 45 min of partial (70%) liver ischaemia and at 3 and 24 h of reperfusion. Controls included ischaemia-reperfusion (I/R) only, sham and bucillamine alone (without ischaemia reperfusion). Liver injury was assessed by serum transaminases (AST and ALT). Sinusoidal blood flow and hepatocyte apoptosis were measured using intravital microscopy (IVM).

Results:

The hepatocellular injury of I/R produced a markedly elevated serum AST which was reduced with bucillamine (2072.5 ± 511.79 vs. 932 ± 200.8, P < 0.05) at 3 h reperfusion. Bucillamine treatment with I/R also increased parenchymal blood flow [red blood cell (RBC) velocity 242.66 ± 16.86 vs. 181.11 ± 17.59, at the end of 3 h of reperfusion) and reduced hepatocyte necrosis/apoptosis at 3 h as well as 24 h (P > 0.001).

Conclusion:

Bucillamine reduces the hepatocellular injury of liver ischaemia reperfusion and improves parenchymal perfusion.