Anticancer potency of Egyptian venom snakes on MCF-7 and HepG2 carcinoma cells.

Breast and hepatic cancers are the leading incidences in the globe occurring of the human sufferings from various cancers. Snake venoms have been reported to provide effective therapeutic agents. The current study investigates the anticancer potency of Egyptian venoms snakes on two cells: breast cancer cells (MCF-7) and hepato-cancer cells (HepG2) (In vitro assay). The examined venoms were more potent on MCF-7 than HepG2 cells. Their inhibition % on MCF-7 ranged from 71.47 to 99.02% with medium inhibition concentrations (IC50s): 3.48, 3.60, 3.70, 4.33, and 4.49 µg/ml for venoms: Echis pyramid (E.H), Cerastes vipera (C.V), Naja haje (N.H), Echis coloratus (E.C), and Cerastes cerastes (C.C), respectively. The values of IC50s on HepG2 were 4.32, 17.77, 59.72, 63.75, and 217.90 µg/ml for toxins: E.C, E.P, C.V, C.C, and N.H, respectively. Some biomarkers were conducted to investigate the apoptotic effects of toxins into the cells. Increasing profiles of lactate dehydrogenase (LDH) activity and levels of glutathione content (GSH) and malodialdhyde (MDA) as well as repairment of DNA indicated such these actions. So, more reliable investigations on these venoms were needed to provide intelligent therapeutic agent for cancer treatment.

Doxorubicin, L-arginine, or their combination as a prophylactic agent against hepatic carcinoma in mice.

Hepatocellular carcinoma (HCC) is one of the ten most commonly diagnosed cancers. Doxorubicin is an antibiotic used in cancer treatment protocols that has several side effects. L-Arginine is a non-essential amino acid that is used as immune system activation and antitumor drugs. Therefore, the current study was designed to compare using doxorubicin, L-arginine, or their combination as a prophylactic agent against hepatic carcinoma induced by hepatocellular carcinoma cells (HepG2) injection in mice. The mice were divided into five groups: normal mice and mice that received HepG2, doxorubicin and HepG2, L-arginine and HepG2, and doxorubicin, L-Arginine, and HepG2, respectively. Liver function test as, aspartate transaminase (AST) and alanine transaminase (ALT), and alpha-fetoprotein (AFP), caspase 3, interleukin 6 (IL-6), tumor necrotic factor (TNF), lipid peroxidation (NDA), and some antioxidant parameters were determined. A significant increase in AST and ALT, α-fetoprotein, TNF-α, and cytokines IL6 and MDA and a significant decrease in the serum caspase and liver catalase were determined in HepG2-injected mice. Moreover, some large hyperchromatic heptocytes were observed and the percentage of the positive area/field of HepPar-1, the most specific HCC marker, was 9.56%. Interestingly, mice that received doxorubicin, L-arginine, or their combination showed an improvement in some of the previous parameters. The improvement was more prominent with L-arginine administration.

Quercetin modulates age-induced changes in the transcript levels of some apoptosis related genes in the skeletal muscles of male rats

Adverse changes occur gradually in the skeletal muscles with age via continuous exposure to oxidative stress. Quercetin, a member of the flavonoids family, possesses anti-oxidative and radical-scavenging activities. Therefore, this study investigated the role of quercetin to modulate age-induced changes in the transcript levels of some apoptosis-related genes in rat's gastrocnemius muscles, up to 15 months-old. Half of the rats at each age (1, 5, 10 and 15 months old) were given a vehicle and the other half was given 200 mg/kg quercetin for 2 weeks, respectively. With the increase of age, vehicle groups showed hyalinization of the muscle fibers and a decrease of the catalase and an increase of the malondialdehyde levels. Down-regulation of Bcl2 gene and up-regulation of both NF-κB and Bax genes were recorded. Interestingly, quercetin groups showed focal hyalinization of the muscle fibers at both 10th and 15th months old. An increase in the catalase and a decrease in malondialdehyde levels, up-regulation of Bcl2 gene and down-regulation of both NF-κB and Bax genes were recorded. In conclusion, quercetin minimized age-induced alteration in the morphological structure and the expression of the apoptosis-related genes via increasing the antioxidant defense in the gastrocnemius muscle.

Comparative study on the toxic effects of some heavy metals on the Nile Tilapia, Oreochromis niloticus, in the Middle Delta, Egypt.

Heavy metals are the most dangerous hazards affecting aquatic biota in Egypt specially the Nile Tilapia, Oreochromis niloticus, which is an important species in commercial fisheries. Some areas were not fully studied to screen the hazards that may affect this economic fish. Therefore, the present study aimed to evaluate the potential hazards of heavy metals on O. niloticus in Al-Gharbiya Governorate in the Middle delta of Egypt. Water and fish samples were collected from Al-Qased canal, Kafr El-Zayaat Nile, El-Maash canal in Al-Gharbiya Governorate plus a reference site which is a fish farm at the Faculty of Agriculture, Damietta University, Damitta Governorate, Egypt. The results showed a significant increase (p < 0.05) in the lead, zinc, magnesium, manganese, and copper levels while showed a significant decrease (p < 0.05) in the iron level in the water from all the investigated areas. Cadmium level was significantly high (p < 0.05) in Kafr El-Zayaat Nile and EL-Maash canal only. These metals were also accumulated in the fish livers and gills. Consequently, ALT and AST activities and creatinine level were significantly (p < 0.05) high in all the investigated areas. Histopathological examination revealed cytoplasmic and nuclear degeneration in the hepatocytes in all the investigated areas. Renal glomeruli and Bowman's capsule were not completely intact in Al-Qased and El-Maash canals while conspicuous shrinkage of the glomeruli was determined in Kafr El-Zayaat Nile. Furthermore, slight damage in the secondary lamellae was detected in the gill from Al-Qased canal while in the other areas appeared vacuolated or destructed. Finally, spleen sections of fish from different sites showed the absence of melanin pigments and some vacuoles. In conclusion, the Nile Tilapia, Oreochromis niloticus, is affected by the toxic effects of the heavy metals in Al-Gharbiya Governorate in Egypt and this gives an alarm and should be taken into consideration.

Can Stem Cells Ameliorate the Pancreatic Damage Induced by Streptozotocin in Rats?

BACKGROUND: Stem cell therapy holds great promise for the repair of injured tissues and organs, and it is one of the most promising therapies for diabetes mellitus. Therefore, the present study was undertaken to elucidate the antidiabetic effect of both mesenchymal stem cells (MSCs) and insulin-producing cells (IPCs) on streptozotocin (STZ)-induced diabetes in rats. MATERIALS AND METHODS: MSCs were derived from bone marrow of male albino rats. MSCs were characterized morphologically and by Cluster of differentiation (CD-ve34) and (CD+ve105). They were then differentiated into IPCs, and both MSCs and IPCs were infused independently into tail veins of rats with STZ-induced diabetes. RESULTS: MSC and IPC therapy significantly improved the body weight and serum insulin, alpha-amylase, adiponectin, creatinine, total cholesterol, triacylglycerol, interleukin-6, tumour necrosis factor-alpha, liver L-malonaldehyde and glycogen levels in the STZ-induced diabetes model. CONCLUSIONS: Bone marrow-derived MSCs have the capacity to differentiate into IPCs capable of controlling the blood glucose level in rats with STZ-induced diabetes. Furthermore, treatment with MSCs and IPCs can improve aberrant biochemical parameters in an STZ-induced diabetes model.

Effect of the Egyptian propolis on the hepatic antioxidant defense and pro-apoptotic p53 and anti-apoptotic bcl2 expressions in aflatoxin B1 treated male mice.

Aflatoxins are potent hepatotoxic due to their role in producing reactive oxygen species and consequently peroxidative damage. Propolis is a honey bee product known for its antioxidant capacity. The aim of this study was to verify the antioxidant effect of the Egyptian propolis extract (EPE) against aflatoxin B1 (AFB1)-induced hepatotoxicity in mice. Forty eight male mice were divided: first, second and third groups were used as control receiving saline, olive oil and EPE respectively, fourth was AFB1 group, fifth and sixth received EPE post or pre AFB1 treatment, respectively. EPE was given as (0.2mg/kg) 3 times a week. AFB1 was given as a single dose (0.25µg/kg). After 2 weeks, the mice were scarified and biochemical, histopathological and immunohistochemical investigations were assessed. EPE has a high content of total phenolics and alkaloids. The inhibitory concentration 50 (IC50) value for DPPH radical scavenging was 1353.8µg/mL. Pretreatment with EPE improved AFB1-induced hepatotoxicity represented in lowering alanine transaminase, aspartate aminotransferase, alkaline phosphatase, cholesterol, triglycerides, lipid peroxidation and pro-apoptotic p53 expression to 33.48±1.98 IU/ml, 53.00±2.37 IU/ml, 123.50±2.02 IU/ml, 76.50±2.66mg/dl, 54.00±3.03mg/dl, 2.22±0.14 nmol/g and 4.31±2.1 cells/field and raising the reduced glutathione, catalase, superoxide dismutase and anti-apoptotic bcl2 expression to 3.37±1.65 nmol/g, 4.92±0.25 nmol/g, 57±0.91UI/g and 39.7±5.9 cells/field which all had non-significant differences with the control, respectively. In conclusion, EPE can attenuate aflatoxin B1-induced hepatotoxicity in mice.

Assessment of the Toxicity of Sub-chronic Low and High Doses of the Bio-insecticide Spinosad on the Liver, Kidney and the Cerebellum in Male Albino Mice

ABSTRACT Spinosad (SPD) is a highly selective insect control product. However, it was reported that SPD has toxicity toward other non-target organisms. This study was conducted to address the toxic effect of two sub-chronic low and high doses; 35 and 350 mg/kg SPD on some biochemical, histological and immunohistochemical parameters of the liver, kidney and cerebellum. Thirty-six male Swiss mice were divided into three groups of 12 mice each; first group (G1) served as a control, second group (G2) received a low sub-chronic dose of SPD that is equal to 35 mg/kg, and third group (G3) received a high sub-chronic dose of SPD that is equal to 350 mg/kg. The results showed that mice which were received 350 mg/kg SPD showed a significant decrease in the body weight and a significant increase in their relative kidney and spleen weights. They also showed a significant increase in alanine aminotransferase (ALT), triglycerides and urea levels. Histopathological examination showed cytoplasmic degeneration and cell necrosis in the liver and kidney. Immunohistochemical examination showed that cerebellum illustrated several neurodegenerative changes and a down-regulation of synaptophysin-Syp. In conclusion, exposure to a high dose of SPD that is equal to 350 mg/kg could cause a marked toxicity on the liver, kidney and cerebellum in male albino mice.

Anti-diabetic activity of Holothuria thomasi saponin.

BACKGROUND: Diabetes mellitus represents a global health problem. It characterized by hyperglycemia that induces oxidative stress leading to a generation of free radicals. A wide variety of natural products in plants and other marine animals represent antioxidant activity and other health benefits like those of sea cucumber. Therefore, this study aimed to investigate the antidiabetic activity of glycosidic compound - saponin - derived from the Egyptian sea cucumber, Holothuria thomasi. MATERIALS AND METHODS: Saponin has been extracted from the Egyptian sea cucumber and confirmed by hemolysis, Salkowski tests, FT/IR, UV and GC-MS analysis. Eighty white female albino rats were divided into four equal groups. The first two groups of rats; control normal and control normal saponin-treated groups. The last two groups which were made diabetic by intraperitoneal injection of streptozotocin had one diabetic control and the other diabetic group that got 300mg/kg B.wt. of saponin extract after Thirty-five days after diabetes induction and lasted for six weeks. RESULTS: The functional group of saponin extract which established with FT/IR spectroscopy demonstrated the presence of saponin in the extracted materials as shown in the peak of the functional group in relevance to the standard one. The UV spectra revealed that λmax of saponin extract was 282nm which in accordance to the standard saponin. Also, GC-MS analysis indicated that the aglycone part of saponin was methyl esters of octadecanoic acid. Saponin extract significantly decreased serum glucose, α-amylase activity, adiponectin, IL-6, TNF-α concentrations and liver L-MDA. However, serum insulin and liver glycogen levels were significantly increased as compared with the diabetic non-treated groups. The histopathological results supported that saponin extract markedly reduced the degenerative change in ß-cells. CONCLUSIONS: This study, therefore, depicts that the Egyptian Holothuria thomasi, sea cucumber saponin as a hypoglycemic agent with the potential to normalize aberrant biochemical parameters and preserved the normal histological architecture of the islets cells of pancreatic tissues.

Efficacy of Rosmarinus officinalis leaves extract against cyclophosphamide-induced hepatotoxicity.

Context Cyclophosphamide (CTX) is used to treat different cancer types, although it causes severe hepatotoxicity due to its oxidative stress effect. Rosmarinus officinalis, L. (Lamiaceae) has a therapeutic potential against hepatotoxicity due to its antioxidant activity. Objective The objective of this study is to investigate the phytochemical analysis of the methanol extract of Rosmarinus officianalis leaves (MEROL) and its efficacy against CTX-induced hepatotoxicity. Materials and methods The phytochemical analyses were assessed spectrophotometericaly. To assess the MEROL efficacy, 72 Swiss albino mice were divided into six groups. Group 1 was control, groups 2 and 3 included mice which were injected intraperitoneally (i.p.) with 100 or 200 mg/kg of MEROL at days 1, 4, 7, 10, 13 and 16; group 4 was injected (i.p.) with CTX (200 mg/kg) at day 17, groups 5 and 6 were injected (i.p.) with MEROL as groups 3 and 4 followed by 200 mg/kg CTX at day 17, respectively. At day 22, six mice from each group were sacrificed and the others were sacrificed at day 37. Results MEROL has a high content of total phenolics, saponins, total antioxidant capacity and DPPH radical scavenging activity. The median lethal dose (LD50) value of MEROL was 4.125 g/kg b.w. The inhibitory concentration 50 (IC50) value for DPPH radical scavenging was 55 µg/mL. Pretreatment with 100 mg/kg MEROL for 16 d ameliorated CTX-induced hepatotoxicity represented in lowering the levels of the aspartate aminotransferase (AST) and lipid profile and minimizing the histological damage. Conclusions Pretreatment with 100 mg/kg b.w. MEROL mitigated CTX-induced hepatotoxicity due to its antioxidant activity.

Ameliorative effect of propolis against cyclophosphamide-induced toxicity in mice.

CONTEXT: Cyclophosphamide (CTX) is a common anticancer agent used for the treatment of several malignancies. However, upon treatment, it induces severe toxicity due to its oxidative stress capability. Propolis, a natural product collected by honey bees, has shown several biological activities, such as free radical scavenging and antioxidant agent. OBJECTIVE: This study elucidates the protective effects of propolis against CTX-induced changes in mice. MATERIALS AND METHODS: Forty-eight male Swiss albino mice were divided into four groups; group 1 was intraperitoneally (i.p.) injected with 200 µL of phosphate buffer saline (PBS), group 2 was injected with 100 mg/kg/d propolis, group 3 was injected with a single dose of CTX (200 mg/kg), and group 4 was injected with a single dose of CTX (200 mg/kg) followed by propolis (100 mg/kg) for 7 consecutive days. After 12 d, mice were bled and then sacrificed to analyze the hematological, biochemical, and histological parameters. RESULTS: The results indicated that CTX-injected mice showed an increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine and a decrease in the total number of white blood cells (WBCs) and platelets. Moreover, dramatically changes in the histological architectures of the liver and kidney were observed. The mice that were injected with CTX/propolis showed an improvement in the levels of ALT, AST, urea, creatinine, WBCs, and platelets. Moreover, the histological picture of the liver and kidney was significantly improved. CONCLUSIONS: In conclusion, propolis might be considered an effective agent in ameliorating the toxicity resulted from CTX treatment.

Synergistic effect of black tea and curcumin in improving the hepatotoxicity induced by aflatoxin B1 in rats.

Aflatoxin B1 (AFB1) is a toxic compound commonly found as a contaminant in human food. It is carcinogenic due its potential in inducing the oxidative stress and distortion of the most antioxidant enzymes. Since black tea possesses strong antioxidant activity, it protects cells and tissues against oxidative stress. Curcumin (CMN), a naturally occurring agent, has a combination of biological and pharmacological properties that include antioxidant activity. Therefore, the present study was carried out to investigate the possible role of separate and mixed supplementation of black tea extract and CMN in the hepatotoxicity induced by AFB1 in rats. A total of 48: adult male Sprague Dawley rats were randomly divided into eight groups with six rats in each group. Group 1 (normal control) includes rats that received no treatment. Groups 2, 3, and 4 (positive control) include rats that received olive oil, black tea extract, and CMN, respectively. Group 5 includes rats that received AFB1 at a dose of 750 µg/kg body weight (b.w.) dissolved in olive oil. Groups 6, 7, and 8 include rats that received AFB1 along with 2% black tea extract, CMN at a dose of 200 mg/kg b.w., and both black tea extract and CMN at the same previous doses, respectively. After 90 days, biochemical and histopathological examination was carried out for the blood samples and liver tissues. A significant decrease in the antioxidant enzymes and a significant increase in the lipid peroxidation and hydrogen peroxide in the rats treated with AFB1 were observed. Moreover, there were dramatic changes in the liver function biomarkers, lipid profile, and liver architecture. Supplementation of black tea extract or CMN showed an efficient role in repairing the distortion of the biochemical and histological changes induced by AFB1 in liver. This improvement was more pronounced when both CMN and black tea were used together.

p53 and Bcl-2expression in response to boldenone induced liver cells injury.

Boldenone is an anabolic steroid developed for veterinary use. Recently, it is used by bodybuilders in both off-season and pre-contest, where it is well known for increasing vascularity while preparing for a bodybuilding contest. So, the present study was designed to investigate the possible effect of using growth promoter boldenone undecylenate on the rabbit liver tissue. Thirty-two adult New Zealand rabbits were divided into four groups (8 animals each). Control group includes animals that injected intramuscularly with olive oil and dissected after 3 weeks. The experimental groups include animals that receive one, two and three intramuscular injections of 5 mg/kg body weight boldenone, respectively. The animals were dissected after 3, 6 and 9 weeks respectively, where the interval of each dose of boldenon was 3 weeks. Small pieces of the liver tissues were sent for the histopathological examination. Apoptotic p53 and antiapoptotic Bc1-2 proteins were localized immunohistochemically. Histological observations of the liver tissue showed that the sinusoidal congestion was the most prominent feature that extended from the centrilobular to the periportal regions. Hepatocellular vacuolation in the centrilobular region was also detected. Liver immunohistochemical observation showed a significant increase of the apoptotic protein p53 and a significant decrease in the antiapoptotic Bc1-2 proteins. The highest frequency of p53 positive cells was observed in the liver sections of three dose of boldenone injections, while the lowest in control group, also the highest frequency of Bcl-2 positive cells was observed in the liver sections of control group while the lowest in three dose of boldenone injections. The present results investigate that people should be careful if they want to use such steroids to enhance their strength and endurance.