Bradykinin Potentiating Factor Research Articles

Mitigative impact of bradykinin potentiating factor isolated from Androctonus amoreuxi scorpion venom and low doses of γ-irradiation on doxorubicin induced hepatotoxicity through ang II/AMPK crosstalk

In this study, the mitigative impact of bradykinin potentiating factor (BPF) and low doses of γ-irradiation (LDR) were evaluated against doxorubicin (DOX) hepatotoxicity through Ang II/AMPK crosstalk. Rats have received a single dose of DOX (10 mg/kg, i.p.). BPF administration at a dose of 1 μg/g (b.wt./twice a week) was started one week before the administration of DOX and followed throughout the study for another consecutive week where LDR rats were subjected to two low fractions of γ-irradiation; 0.5 Gy/fraction/week up to the cumulative dose of 1 Gy at 7 days before and after doxorubicin administration. DOX produced a remarkable disturbance in serum hepatic enzymes activities, hepatic oxidative stress indices, as well as hepatic inflammatory and fibrotic markers in response to a marked elevation in hepatic angiotensin II (Ang II) together with marked depression in hepatic AMP-activated protein kinase (AMPK) expressions. The combination of BPF and LDR produced a significant improvement in all examined parameters as well as mitigates hepatic toxicity through inhibition of Ang II induced by DOX, which might also be mediated by AMPK activation. Furthermore, histopathological and immunohistochemical examination reinforced the previous results. In conclusion, these findings shed new light on the mechanism underlying the anti-inflammatory and anti-fibrosis consequence of our remedy and support the potential use of it as a preventive and therapeutic candidate against hepatic toxicity through Ang II/AMPK crosstalk.

Effect of a bradykinin potentiating factor separated from honey bee venom on thyroid gland and testis in hypothyroid white rats

BackgroundAnimal venoms have been known as a source of drugs beneficial to human health. Accordingly, this study was designed to determine the effect of bradykinin potentiating factor (BPF) separated from honey bee venom, Apis mellifera on histological structure, thyroid and male sex hormones of the thyroid gland and testis in a model of hypothyroid male white rats induced by carbimazole.ResultsThis study includes male rats divided into 6 main and sub-groups (10 rats in each group). Control group, carbimazole group, levothyroxine group, BPF group, carbimazole group treated with levothyroxine and carbimazole group treated with BPF. At the end of experiments (60 days) rats were sacrificed and dissected; the blood was collected for determination of thyroid and male sex hormones. Also, the thyroid gland and testis were taken to histological study. The results indicated that, carbimazole group showed a highly significant decrease in thyroid hormones (T4, T3, Ft4 and Ft3) and male sex hormones (LH, FSH and testosterone), but a significant increase in TSH compared to control group. The results revealed that, treated groups with levothyroxine or BPF have significant increase in thyroid and male sex hormones and significant decreasein TSH. A significant improvement was detected in co-treated groups (hypothyroid groups) with levothyroxine or (BPF). Also, the present study showed a histopathological change in thyroid gland and testis of hypothyroid male rats.ConclusionTreated hypothyroid rats with levothyroxine as a drug and BPF as a natural product showed an improvement of these complications induced by carbimazole in thyroid gland and testis. Therefore, BPF may be benefical in treatment of hypothyroidism.

Scorpion bradykinin potentiating factor mitigates lung damage induced by γ-irradiation in rats: Insights on AngII/ACE/Ang(1–7) axis

The goal of this research is to study the mitigating impact of bradykinin potentiating factor (BPF) found in scorpion Androctonus bicolor venom on irradiation-induced lung damage as a new functional target for angiotensin-converting enzyme inhibitors (ACEIs).Male rats were exposed to 7 Gy of γ-radiation as a single dose, with a biweekly intraperitoneal injection of 1 μg/g BPF.Gamma irradiation not only boosted the ACE activity and angiotensin II (Ang II) level, in lung tissue but also significantly depressed the angiotensin (1–7) (Ang (1–7)) that, lead to lung toxicity through a significant elevation of pulmonary levels of CXC-chemokine receptor 4 (CXCR4), toll-like receptor 4 (TLR4), nitric oxide (NO) and lactate dehydrogenase (LDH) activity with a marked disruption in oxidative stress markers, via a reduction in the level of total thiol (tSH) and superoxide dismutase (SOD) activity associated with an elevation in protein carbonyl (PCO) contents. In addition, apoptotic consequences of gamma irradiation were evidenced by raising the levels of mitogen-activated protein kinase (MAPK), C-Jun N-Terminal Kinases (JNK), and cleaved caspase-3.BPF administration leads to ACE inhibition, consequently sustaining decreased Ang II alongside increased Ang (1–7) production. Those sensitive molecules reduce irradiated lung issues.In conclusion, BPF significantly diminished the biochemical and histopathological consequences of radiation through renin-angiotensin system (RAS) control and ACE suppression in the lung.

Reform of Hematopoietic, Apoptotic and Oxidative Disturbance Induced by Accumulated γ-Irradiation in Rat’s Bone Marrow via Curative Efficacy of Bradykinin Potentiating Factor Isolated from Bee Venom

Reform of Hematopoietic, Apoptotic and Oxidative Disturbance Induced by Accumulated γ-Irradiation in Rat’s Bone Marrow via Curative Efficacy of Bradykinin Potentiating Factor Isolated from Bee Venom

Concerted hepatoprotective effect of bradykinin potentiating factor and low dose of γ- radiation on Naja haje envenomed rats via Bax/Bcl2 pathway

This study investigates the concerted hepatoprotective effects for three doses of bradykinin potentiating factor (BPF) and/or followed by exposure to a low dose of γ-radiation (LDR) against Naja haje envenoming in rats. Male rats were injected with three consecutive doses of BPF (1 μg/g i.p. for 3 days), followed by exposure to a low dose of gamma radiation (0.5 Gy), and then rats were injected with a dose of Naja haje venom (250 μg/kg i.p.). Results showed that Naja haje causes liver damage, significant elevation of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), cytochrome c, Nitric oxide (NO), malondialdehyde (MDA) and significant depletion in glutathione peroxidase (GPx) contents. In addition, significant depletion in B-cell lymphoma 2 (Bcl-2) and significant elevation in BcL-2 associated X (Bax protein), nuclear factor kappa B (NF-κB), interleukin-1β (IL-1β) in hepatocytes. Bradykinin potentiating factor and/or low dose of γ-radiation caused improvement in liver damage caused by Naja haje venom by a significant decrease in ALT, AST, ALP levels, Bax, cytochrome c, NF-κB, IL-1β, NO and MDA contents, BPF alone or combined with low dose radiation caused a significant increase in Bcl2 and GPx contents. In conclusion, the concerted impact of BPF and LDR may provide an effective venom detoxification tool that helps to reduce hepatic toxicity and extends the lifespan.

Ameliorative effects of bradykinin potentiating factor, butylated hydroxy toluene and oltipraz on biochemical and histological structure of lymphoid organs in aflatoxicated female rats

Ameliorative effects of bradykinin potentiating factor, butylated hydroxy toluene and oltipraz on biochemical and histological structure of lymphoid organs in aflatoxicated female rats

Ameliorative effects of bradykinin potentiating factor, butylated hydroxy toluene and oltipraz on biochemical and histological structure of lymphoid organs in aflatoxicated female rats

Ameliorative effects of bradykinin potentiating factor, butylated hydroxy toluene and oltipraz on biochemical and histological structure of lymphoid organs in aflatoxicated female rats

Comparative ameliorative actions of extracted bradykinin potentiating fraction from cobra snake venom and synthetic antioxidants on hepatic tissue of aflatoxicosed rats

ABSTRACT Mycotoxins are secondary metabolites produced by Aspergillus, Penicillium and other genera which contaminate food and exhibit hazardous effects on humans and animals. Aflatoxins (AFs) caused liver necrosis, fibrosis. In the present study, we planned to evaluate the action of bradykinin potentiating factor (BPF) extracted from Egyptian cobra snake venom and synthetic antioxidants; butylated hydroxytoluene (BHT) and oltipraz (OPZ) on the hepatic tissue of aflatoxicosed rats. Aflatoxicosis caused a significant increase of nitric oxide (NO) and lipid peroxidation as malondialdehyde (MDA) associated with a significant decrease in the level of total thiols, glutathione (GSH), and the activities of glutathione peroxidase (GPx) and transferase (GST). In addition to a decrease in the counts of white blood cells (WBCs), lymphocytes (LYM), monocytes (MONO), eosinophils (EOS), red blood cells (RBCs) and an increase in neutrophil counts (NEUT) as well as a significant decrease in the gene expression of hepatic interleukin-1β (Il-1β). The previous changes were confirmed by histopathological alterations. Treatment of aflatoxicosed rats with any of BPF, BHT or OPZ resulted in amelioration of the oxidative stress parameters, blood picture and hepatic IL-1β with improvement in histological features. In conclusion, either BPF, BHT or OPZ can be used for the treatment of aflatoxicosis.

Bradykinin-potentiating factor isolated from Leiurus quinquestriatus scorpion venom alleviates cardiomyopathy in irradiated rats via remodelling of the RAAS pathway.

The objective of this work was to evaluate the effect of a bradykinin-potentiating factor (BPF) isolated from Leiurus quinquestriatus scorpion venom as a natural modulator of radiation-induced cardiac damage. Four groups of rats were treated as follows; control group, group receiving BPF (1µg/g b.wt i.p./biweekly) for 4weeks, group irradiated at 6Gy, group receiving BPF post-irradiation for 4weeks. Irradiation induced a significant elevation of myocardial parameters: atrial natriuretic peptide (ANP), cardiac troponin I (cTnI), potassium (K+ ) and creatine kinase (CK); vascular indices: lactate dehydrogenase (LDH), inducible nitric oxide synthase (iNOS) and endothelin I; oxidative stress indices: malondialdehyde (MDA) associated with a significant depletion of both reduced glutathione (GSH) in the cardiac tissue homogenate and serum ferric reducing antioxidant power (FRAP) depletion and significantly reinforced elevation of Renin Angiotensin Aldosterone System (RAAS) indices: serum angiotensin II (AngII) and aldosterone, and also protein expression of cleaved caspase-3 and cyclophilin A. BPF administration altered the biochemical damage of radiation, specifically inhibited AngII formation, aldosterone release and prevented the histopathological and immunohistochemical alterations which were observed in cardiac tissue with significant reduction in mean arterial blood pressure (MAP) caused by irradiation. In conclusion, biochemical assays, histopathological and immunohistochemical findings of the present study demonstrated that exogenous BPF isolated from scorpion venom reduced the cardiomyopathy alterations induced by irradiation via remodelling of the RAAS pathway.

Hepatotoxicity effect of short-term Bradykinin potentiating factor in cholestatic rats

BackgroundDrug-induced hepatotoxicity is an extremely widespread condition and is responsible for a variety of pathological effects on the liver. It was reported that hepatotoxicity induced by angiotensin converting enzyme inhibitors (ACEIs) is cholestasis mediated hepatitis. Bradykinin-potentiating factor (BPF) is one of the natural ACEIs. Although prolonged treatment with ACEIs provides protection against liver injury, the effect of short-term treatment with ACEIs has not been fully elucidated before. Thereby, the present study sought to determine if transient ACE inhibition may exacerbate the hepatotoxicity caused by bile duct ligation (BDL) in rats. MethodsTwenty one Wistar rats were divided into 3 groups: Sham-operated group, bile duct ligated (BDL) rats, and BDL rats treated for short-term with BPF (1 μg/kg body weight) day after day for one week and biochemical parameters were measured. Also, we assessed expression level of ACE1 and detection of hepatotoxicity in the liver tissues of different groups. ResultsThere was a significant increase in liver enzymes, bilirubin levels, and oxidative stress in the BDL group after treatment with BPF as compared to BDL group. We found overexpression of ACE1 gene in BDL group compared to BPF and Sham-operated control group. Histopathological examination of liver treated with BPF showed severe degeneration hepatic architecture and hepatocytes as compared to BDL group. Collagen deposition increased after BPF treatment as compared to BDL groups. ConclusionThe present investigation suggests and recommends that short- term ACE inhibition pathway potentiates liver fibrosis during cholestasis disease.

Ameliorative effect of bee venom and its extracted bradykinin-potentiating factor on neurological alteration induced by acrylamide and chips administration

BackgroundAcrylamide is reported for its toxicity on the central and the peripheral nervous system and causes paralysis. Bee venom (BV) and bradykinin-potentiating factor (BPF) have been documented for their potential therapeutic effects as anti-neuroinflammation. The study aimed to ameliorate the neurotoxic effects of acrylamide or chips by using BV or its extracted BPF. Mice were divided into 15 subgroups: control (G1.1, G1.2, G1.3) at 30, 45, and 60 days, respectively; acrylamide- (10 mg/kg b.w.; orally daily) administered subgroup for 30 days (G2.1), 45 days (G2.2), and 60 days (G2.3); chips feeding group (1/3 of daily diet) for 30 days (G3.1), 45 days (G3.2), and 60 days (G3.3); bee venom-treated group for 60 days (1.319 mg/kg b.w.) (G4.1); BPF-treated group for 60 days (2.314 mg/kg b.w.) (G4.2), day after the other day; and acrylamide- or chips-administered groups combined either with BV (G5.1, G6.1) or BPF treatment (G5.2, G6.2) for 60 days.ResultsThe results indicated that the approximate LD50 for BV and BPF equal to 13.19 mg/kg and 23.14 mg/kg, respectively, and the extracted BPF contains 15 amino acids. Also, the results showed abnormal gait in mice of acrylamide-administered groups which was accompanied by histopathological changes in the hippocampus, cerebellum, and cerebral cortex. A marked gradual increase of alpha-synuclein expression was noted at the studied region in the acrylamide- and chips-treated groups at 60 days of treatment as compared to control. Both BV- and BPF-treated groups either separately or in co-administration with acrylamide or with chips did not show any histopathological changes in the studied regions with downregulated expression of alpha-synuclein.ConclusionThe study concluded the neuroprotective effect of BV and its extracted BPF against neurotoxicity induced by acrylamide or chips administration.

Counter effect of bee venom and its extracted bradykinin-potentiating factor on acrylamide and chips administration-induced complications in the liver and kidney of male mice

BackgroundAcrylamide has been reported to induce hepato- and nephrotoxicity. The present investigation aims to alleviate the dangerous effects at the histopathological and physiological levels of acrylamide by bee venom and its extracted bradykinin-potentiating factor (BPF). Seventy-five adult male mice were divided into 15 groups: a control (G1) 15 animals for 30 (G1.1), 45 (G 1.2), and 60 (G 1.3) days of experimental periods; acrylamide-administered G2.1, G2.2, and G2.3 received acrylamide orally (10 mg/kg b.w) daily for 30, 45, and 60 days. Chips-administered G3.1, G3.2, and G3.3 were fed one third of its daily diet by chips for 30, 45, and 60 days. Bee venom- and BPF-treated G4.1 and G4.2 were i.p. injected with bee venom (1.319 mg/kg b.w.) and BPF (2.314 mg/kg b.w.), respectively, day after the other day for 60 days. G5.1 and G5.2 received acrylamide orally (10 mg/kg b.w) combined either with i.p. by bee venom (1.319 mg/kg b.w.) or BPF (2.314 mg/kg b.w.) respectively day after the other day for 60 days. G6.1 and G6.2 were fed one third of its daily diet by chips for 60 days combined either with i.p. by bee venom (1.319 mg/kg b.w.) or with BPF (2.314 mg/kg b.w.), respectively, day after the other day for 60 days.ResultsThe results showed that acrylamide administration and chips feeding groups suffer from alteration and histopathological changes in liver and kidney tissues that were accompanied with the increase in liver and kidney physiological biomarker (ALT, AST, urea, creatinine, uric acid) and the decrease in the albumin levels. Acrylamide or chips combined with either bee venom or BPF showed improvement in the level of physiological and histopathological studies.ConclusionThe study concluded the protective role of bee venom and its extracted BPF against acrylamide- and chips-induced hepato- and nephrotoxicity.

Antioxidant Effects of Bradykinin Potentiating Factor (BPF) Isolated from Scorpion Venom in Liver Injury Induced by Carbon Tetrachloride (CCl4) in Male Albino Rats

The main purpose of this study is to evaluate the ability of bradykinin potentiating factor (BPF) isolated from scorpion venom (Leiurus quinquestriatus) in treatment of liver injuries which induced by injection of CCl4 in male Albino rats. Male Albino rats (250±20 g body weight) were divided into four groups. In the control group; Albino rats were intraperitoneally (i.p) injected with 100 L saline solution. The second group (i.p) injected with BPF in 100 L saline solutions (1 gm/g. b. w. per 5 days). Third and fourth groups were i.p. injected with 0.5 ml/kg body weight (b. w.) twice weekly of CCl4 for fifteen days, after that only the fourth group was treated by BPF in 100 μL saline solutions (1 μgm/g. b. w. per 5 days). The results indicated that, CCl4 injection induced a significant decrease in serum catalase (CAT), Superoxide Dismutase (SOD), reduced glutathione (GSH), total protein and albumin, within thirty days post-injection of CCl4 as compared to the normal control group. In contrast, CCl4 induced a significant increase in Malondialdehyde (MDA), Aspartate Amino Transferase (AST), Alanine Amino Transferase (ALT), and Alkaline Phosphatase (ALP) compared to normal control animals. The efficiency of BPF treatment is alleviation the effects of CCl4 on these parameters. The improvement of these parameters may be attributed to the release antioxidant and cytokines and/or amelioration of the toxic effects of CCl4 on the liver.

Effect of a bradykinin-potentiating factor isolated from scorpion venom (Leiurus quinquestriatus) on some blood indices and lipid profile in irradiated rats.

Bradykinin appears to be an important regulator of cardiovascular function. It is also being increasingly noted as a participant in actions of drugs that affect the liver, kidney, and circulation. In our previous studies, bradykinin-potentiating factor (BPF) isolated from scorpion venom (Leiurus quinquestriatus) has been shown to be protective against hepato- and nephrotoxicity as well as healing skin burns by reducing oxidative stress in hyperglycemic conditions. Therefore, we aim to evaluate the ability of BPF in treating irradiated rats. A group of rats was exposed to γ-irradiation and subsequently treated with BPF injections aiming to elucidate the possibility of BPF to rescue γ-irradiation harmful effects. As controls, we used γ-irradiation exposed, BPF-injected, and untreated rats. The data obtained showed that the irradiated animals suffered from marked changes of many important blood parameters including red blood cells, leukocytes, platelets, hemoglobin, packed cell volume, high-density cholesterol, total cholesterol, triglycerides, and low-density cholesterol. Interestingly, BPF was able to rescue the deleterious effects of irradiation in rats and normalized their blood parameters to the basal levels. We conclude that BPF could ameliorate irradiation damaging effects.

Hepato- and nephroprotective effects of bradykinin potentiating factor from scorpion (Buthus occitanus) venom on mercuric chloride-treated rats.

Bioactive peptides such as bradykinin potentiating factor (BPF), have, anti-oxidative, anti-inflammatory, immunomodulatory and ameliorative effects in chronic diseases and play a potential role in cancer prevention. It is known that the liver and kidney accumulate inorganic mercury upon exposure, which often leads to mercury intoxication in these organs. In this study, we investigated the effect of bradykinin potentiating factor (BPF), a scorpion venom peptide, on mercuric chloride-induced hepatic and renal toxicity in rats. We used 20 adult male Albino rats divided into four equal groups: the first group was injected with saline (control); the second group was administered daily with mercuric chloride (HgCl2) for 2 weeks; the third group was administered with BPF twice weekly for 2 successive weeks, while the fourth group was exposed to BPF followed by HgCl2. We observed that HgCl2 treated rats had a significant increase in serum ALT, AST, ALP, creatinine and urea levels compared to control. Furthermore, HgCl2 treated rats showed a marked decrease in total proteins, albumin and uric acids compared to control. The previously studied parameters were not significantly changed in BPF pretreated rats compared to control. Moreover, a significant decrease in the activities of glutathione perioxidase (GSH), superoxide dismutase (SOD), and catalase (CAT), in addition to a significant increase in the level of malondialdehyde (MDA) were observed in hepatic and renal tissues of rats after HgCl2 treatment. In contrast, the HgCl2/BPF treated rats showed a significant elevation in the activity of GSH, SOD, and CAT accompanied with a significant regression in the level of MDA compared to the HgCl2 exposed rats. We conclude that treatment with BPF is a promising prophylactic approach for the management of mercuric chloride-induced hepato- and nephro-toxicities.

Comparative Effects of Scorpion Venom and Aqueous Basil (Ocimum basilicum) Leaves Extracts on Ccl4-induced Toxicity in Albino Rats

The present study aims to compare the therapeutic effects between to extract scorpion venom (bradykinin potentiating factor; BPF) and aqueous extract of Sweet basil (Ocimum basilicum) on CCl4-induced toxicity of liver and kidney in albino rats. Rats were divided into 8 groups. Group (1) was served as normal group; Group (2) was injected intraperitoneal (i.p.) once a week for 3 weeks with BPF at a dose (1 μgm/g). Group (3) was received orally O. basilicum extract, twice a week for 6 weeks at dose (20 ml/kg). Group 4 was treated with the same doses of BPF and O. basilicum. Group (5) was injected i.p. with CCl4 (1 ml/kg), 3 times weekly, for 2 weeks and served as control group. Groups 6, 7 and 8 were injected i.p. with CCl4 then treated i.p. with BPF, orally with O. basilicum and BPF plus O. basilicum respectively. The results of the present study cleared that normal group (1) and groups (2, 3 and 4) showed no significant difference in all liver and kidney functions, besides antioxidant enzymes except creatinine and GSH, were highly significant increase in group (4). CCl4 caused a highly significant decrease in serum albumin, uric acid, besides Catalase, GSH, SOD activities in liver tissue, while there are an elevation in serum AST, ALT, ALP, γ-GT, creatinine and Urea, besides MDA and NO levels in liver tissue. While, groups (6, 7 and 8) revealed reverse effect in all parameters and recorded a remarkable improvement, comparing with normal group. It can be concluded that the treatment with the extract from the scorpion venom Buthus occitanus (BPF) is more effective than those of extract from the plant (O. basilicum) against the toxicity of liver and kidney-induced by CCl4 in albino rats. In addition, the hepato-ameliorating and antioxidant effects of two extracts were found to be better than those of extract of BPF or O. basilicum indepently.

Biochemical Effects of Bradykinin Potentiating Factor (BPF) Isolated from Scorpion Venom ( Leiurus quinquestriatus) against CCl4- Liver Injury in Male Albino Rats.

The main purpose of this study is to evaluate the ability of bradykinin potentiating factor (BPF) isolated from scorpion venom (Leiurus quinquestriatus) in treatment of liver injuries which induced by injection of CCl4in male Albino rats. Male Albino rats (250±20 g. body weight) were divided into four groups. In the control group; Albino rats were interaperitoneally (i.p) injected with 100 µL saline solution. The second group (i.p) injected with BPF in 100 µL saline solutions (1μgm/g. b. w. per 5 days). Third and fourth groups were i.p. injected with 0.5 ml/kg body weight (b. w.) twice weekly of CCl4 for fifteen days, after that only the fourth group was treated by BPF in 100 µL saline solutions (1μgm/g. b. w. per 5 days). The results indicated that, CCl4 injection induced a significant decrease in serum catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), total protein and albumin, within thirty days post-injection of CCl4 as compared to the normal control group. In contrast, CCl4 induced a significant increase in malondialdehyde(MDA), aspartate amino transferase (AST), alanine amino transferase (ALT), and alkaline phosphatase (ALP) compared to normal control animals. The efficiency of BPF treatment is alleviation the effects of CCl4 on these parameters. The improvement of these parameters may be attributed to the release antioxidant and cytokines and/or amelioration of the toxic effects of CCl4 on the liver.

Temperature dependence of cardiac sarcoplasmic reticulum and sarcolemma in the ventricle of catfish (Clarias gariepinus)

The present study was undertaken to examine the relative contribution of the SR-Ca2+ release and sarcolemmal Ca2+ channels in developing the cardiac force at two different temperatures (20 and 30°C) in the catfish (Clarias gariepinus).The sarcolemmal Ca2+ contribution of activator Ca2+ was greater at a test temperature of 30°C as assessed by verapamil. Whereas the SR-Ca2+ contribution was higher at 20 and 30°C and a frequency rate of 0.2 and 0.4Hz as assessed by caffeine and adrenaline, respectively. Bradykinin potentiating factor (BPF7) which was isolated from jelly fish (Cassiopea andromeda) decreased the cardiac force developed at a frequency rate of 0.2Hz and a temperature of 20°C, whereas it increased the force developed at frequency rates of 0.2 and 0.4Hz at 30°C. These results indicate that BPF7 may act like verapamil in reducing the cardiac force through blocking the sarcolemmal Ca2+ channels at low temperature and like adrenaline in an increase of the cardiac force developed at warm temperature and the high frequency rate through stimulation of SR-Ca2+ activator. Therefore, this study indicates that the sarcolemmal Ca2+ influx and the SR-Ca2+ release contributors of activator Ca2+ for cardiac force development in the catfish heart were significantly greater at warm temperature and at the pacing frequency rates of 0.2 and 0.4Hz as assessed by verapamil, adrenaline, caffeine and BPF7. However, the relative contribution of the sarcolemmal Ca2+ influx in the development of cardiac force in the catfish heart was greater than that of SR-Ca2+ release.

Prevention of hepatic and renal toxicity with bradykinin potentiating factor (BPF) isolated from Egyptian scorpion venom (Buthus occitanus) in gentamicin treated rats

The present investigation report the effect of a bradykinin-potentiating factor (BPF) on gentamicin-induced oxidative stress in rat liver and kidney. BPF is a peptide fraction isolated from the venom of the Egyptian scorpion (Buthus occitanus) has been demonstrated to have antioxidant, free radical scavenger and anti-inflammatory effects. Thirty male Rattus norvegicus (130–150g) were included and divided into three equal groups as follows: Group I (control), group II was (ip) injected with gentamicin alone (80mg/kg/day) for 15days, group III was given (ip) injection of BPF (1mg/kg/day) one hour prior to gentamicin treatment for 15days with the same dose of gentamicin as group II. Both organs were subjected to histopathological analysis with the light microscope. The activities of alanine aminotransferase (ALT), asparate aminotransferase (AST) and alkaline phosphatase (ALP) in serum were measured as indicators of the liver function. As parameters of the kidney function, creatinine, uric acid and urea concentrations were determined. Also, malondialdehyde (MDA), reduced glutathione (GSH), super oxide dismutase (SOD) and catalase (CAT) were determined in both tissues. Gentamicin caused a significant decrease or inhibition in the activities of GSH, SOD, and CAT, with significant increase in the level of MDA, ALT, AST, ALP, as well as creatinine, uric acid and urea concentrations in versus to control groups in both liver and kidney. Co-administration of gentamicin and BPF significantly increased the activity of GSH, SOD, and CAT, with significant decrease in the level of MDA and maintained serum (ALT); (AST); (ALP), creatinine, uric acid and urea concentrations as the same level as control group. Moreover, administration of gentamicin resulted in damage to liver and kidney structures. Administration of BPF before gentamicin exposure prevented severe alterations of biochemical parameters and disruptions of liver and kidney structures. In conclusion, this study obviously demonstrated that pretreatment with BPF significantly attenuated the physiological and histopathological alterations induced by gentamicin. Also, the present study identifies new areas of research for development of better therapeutic agents for liver, kidney, and other organs dysfunctions and diseases.

Immune modulating effects of malathion with the role of bradykinin potentiating factor in juvenile male rats

Background: The use of malathion as an insecticide, is accompanied by the appearance of many adverse effects. Objective: To verify the immunological characteristics of malathion and to determine whether Bradykinin Potentiating Factor (BPF) is able to counteract these effects, and to emphasize the affected pathophysiological mechanisms. Material and methods: Juvenile rats were divided into three groups: animals received a vehicle (control group), malathion (malathion group), or malathion then BPF (BPF group). Each group included three subgroups, which were sacrificed two days after two, four, and six weeks of malathion exposure respectively. BPF subgroups were exposed to malathion, then treated with single, double, and triple successive IP injections of BPF respectively. Results: The concentration of total globulin, total immunoglobulins, IgG, IgM, circulatory immune complexes, total number of RBC & platelets, and hemoglobin concentrations decreased significantly in malathion-exposed animals. The number of total leucocytes and lymphocytes increased. Histopathological changes of bone marrow and spleen after malathion exposure were consistent with these findings. Recovery of bone marrow and splenic changes, normalization of peripheral blood elements, reduction of elevated proinflammatory markers (IL-2, IL-4 and TNF-α), total plasma peroxide and oxidative stress index (OSI) while increased total antioxidant capacity (TAC) were observed after double and triple injections of BPF. Our results suggest that exposure to malathion has negative effects on immune function that was mediated through alteration of cytokines, antioxidants and direct damage of BM. Also, BPF can ameliorate both physiological and morphological changes.