Immuno-antioxidative reno-modulatory effectiveness of Echinacea purpurea extract against bifenthrin-induced renal poisoning.

This study was conducted to evaluate the ameliorative, anti-inflammatory, antioxidant, and chemical detoxifying activities of Echinacea purpurea ethanolic extract (EEE) against bifenthrin-induced renal injury. Adult male albino rats (160-200 g) were divided into four groups (10 rats each) and orally treated for 30 days as follows: (1) normal control; (2) healthy animals were treated with EEE (465 mg/kg/day) dissolved in water; (3) healthy animals were given bifenthrin (7 mg/kg/day) dissolved in olive oil; (4) animals were orally administered with EEE 1-h prior bifenthrin intoxication. The obtained results revealed that administration of the animals with bifenthrin caused significant elevations of serum values of urea, creatinine, ALAT and ASAT, as well as renal inflammatory (IL-1ß, TNF-α & IFN-γ), apoptotic (Caspase-3) and oxidative stress (MDA and NO) markers coupled with a marked drop in the values of renal antioxidant markers (GSH, GPx, and SOD) in compare to those of normal control. Administration of EEE prior to bifenthrin resulted in a considerable amelioration of the mentioned deteriorated parameters near to that of control; moreover, the extract markedly improved the histological architecture of the kidney. In conclusion, Echinacea purpurea ethanolic extract has promising ameliorative, antioxidant, anti-inflammatory, renoprotective, and detoxifying efficiencies against bifenthrin-induced renal injury.

Echinacea purpurea extract intervention for counteracting neurochemical and behavioral changes induced by bifenthrin.

This study was conducted to elucidate the possible protective efficiency of Echinacea purpurea hydroethanolic extract (EchEE) against bifenthrin (BIF)-induced neuro-chemical and behavioral changes in rats. Total phenolics content, reducing power and radical scavenging activity of EchEE were estimated. Four groups of adult male albino rats were used (10 rats each) as follows: 1) Control healthy rats ingested with placebo, 2) Healthy rats orally received EchEE (465 mg/kg/day), 3) Rats intoxicated with BIF (7mg/kg/day) dissolved in olive oil, and 4) Rats co-treated with EchEE (465 mg/kg/day) besides to BIF (7mg/kg/day) intoxication. After 30 days, some neuro-chemical and behavioral tests were assessed. The behavioral tests revealed that rats received BIF exhibited exploratory behavior and spatial learning impairments, memory and locomotion dysfunction, and enhanced anxiety level. Biochemical findings revealed that BIF induced-oxidative stress in the cortex and hippocampus; this was appeared from the significant rise in malondialdehyde (MDA) and nitric oxide (NO) levels, coupled with decreased catalase (CAT), superoxide dismutase (SOD), paraoxonase-1 (PON-1) activities, and reduced glutathione (GSH) level in both brain areas. Also, BIF induced a significant increase caspas-3, tumor necrosis factor alpha (TNF), and interleukin-1beta (IL-1ß) in both areas; dopamine and serotonin levels, and ACh-ase activity were markedly decreased in both areas. Interestingly, treatment of rats with EchEE in combination with BIF resulted in a significant decrease in oxidative stress damage, and modulation of the apoptotic and pro-inflammatory markers. Also, EchEE markedly improved behavioral activities and neurotransmitters level that were impaired by BIF. In conclusion, the present study clearly indicated that EchEE can attenuate brain dysfunction induced by pesticides exposure through preventing the oxidative stress. This may be attributed to its high antioxidant component.

Therapeutic efficacy of α-lactalbumin coated oleic acid based liposomes against colorectal carcinoma in Caco-2 cells and DMH-treated albino rats.

Colorectal cancer (CRC) is a malignant tumor recognized as a major cause of morbidity and mortality throughout the world. Therefore, novel liposomes of oleic acid coated with camel α-lactalbumin (α-LA coated liposomes) were developed for their potential antitumor activity against CRC, both in vitro and in DMH-induced CRC-modeled animal. In vitro results indicated the high safety of α-LA coated liposomes towards normal human cells with potent antitumor activity against Caco-2 cells at an IC50 value of 57.01 ± 3.55 µM with selectivity index of 6.92 ± 0.48. This antitumor activity has been attributed to induction of the apoptotic mechanism, as demonstrated by nuclear condensation and arrest of Caco-2 cells in sub-G1 populations. α-LA coated liposomes also revealed a significant up-regulation of the p53 gene combined with a down-regulation of the Bcl2 gene. Moreover, in vivo results revealed that treatment of induced-CRC modeled animals with α-LA coated liposomes for six weeks markedly improved the CRC-disorders; this was achieved from the significant reduction in the values of AFP, CEA, CA19.9, TNF-α, IL-1ß, MDA, and NO coupled with remarkable rise in SOD, GPx, GSH, CAT, and CD4+ levels. The histopathological findings asserted the therapeutic potential of α-LA coated liposomes in the treatment of CRC. Therefore, the present results proved the antitumor activity of α-LA coated liposomes against CRC through the restoration of impaired oxidative stress, improved immune response, and reduced inflammation.Communicated by Ramaswamy H. Sarma.

In Vitro and In Vivo Synergistic Antitumor Activity of Albumin-Coated Oleic Acid-Loaded Liposomes toward Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers, closely associated with cirrhosis and fibrosis. This study aimed to assess the antitumor activity of oleic acid-liposomes (uncoated liposomes) upon coating with albumin against HCC. The in vitro studies revealed the high safety of the prepared uncoated and albumin-coated liposomes to normal HFB-4 cells (EC100 of 35.57 ± 0.17 and 79.133 ± 2.92 µM, respectively) with significant anticancer activity against HepG-2 cells with IC50 of 56.29 ± 0.91 and 26.74 ± 0.64 µM, respectively. The albumin-coated liposomes revealed superior apoptosis induction potential (80.7%) with significant upregulation of p53 gene expression (>7.0-fold), compared to OA. The in vivo study revealed that the administration of uncoated or albumin-coated liposomes (100 mg/kg) for six weeks markedly retarded the DENA-induced HCC in Wistar albino rates through regulating the liver enzymes, total bilirubin level, pro-inflammatory cytokines, and oxidative stress. Accordingly, the current study supports the in vitro and in vivo chemo-preventive feature of albumin-coated liposomes against HCC through modulation of apoptosis, improvement of the immune response, reduction of inflammation, and restoration of impaired oxidative stress, which is the first reported to the best of our knowledge.

Hormonal and inflammatory modulatory effects of hesperidin in hyperthyroidism-modeled rats.

The goal of the current study was to investigate the hormonal modulatory efficiency of hesperidin, through its regulatory potential of immunological, inflammatory, and/or antioxidant changes in on hyperthyroidism modeled adult female albino rats. Both normal and hyperthyroidism modeled rats (140-160g) were randomly divided into four groups (10 animals each) as follows: 1) healthy animals were daily ingested with saline for six weeks, and served as control group, 2) healthy animals were intraperitoneally injected with hesperidin (50 mg/kg/day) for a similar period, 3) hyperthyroidism-modeled animals without any treatment acted as positive control, and 4) hyperthyroidism-modeled animals were treated intraperitoneally with hesperidin for a similar period. The findings showed that hesperidin significantly modulated hyperthyroidism deteriorations, this was evidenced by a remarkable decline in serum T4, FT4, T3, FT3, TNF-α, IL1ß-, IL4-, IL-6, and IL-10 levels, with a minor increase in TSH and significant raise in CD4+ level. Similarly, valuable improvement was observed in the oxidative status; serum SOD, GPx, CAT, and GSH levels were dramatically enhanced, associated with remarkable drop in MDA and NO levels. Also, hesperidin demonstrated nephro-hepatoprotective and anti-atherogenic potential, this was achieved from the notable reduction in ALAT and ASAT activities as well as urea, creatinine, cholesterol, and triglyceride close to the corresponding values of healthy group. These findings were supported by histological and immunohistochemical ones that showed a notable decrease in the expression of the calcitonin antibody. In conclusion, hesperidin possesses anti-hyperthyroidism, immunoinflammatory regulatory, and antioxidant activities that evidenced from the improvement of physio-architecture of the thyroid gland, reduction of inflammation and restoration of the impaired oxidative stress. This effect might be mechanized through immunological, inflammatory, apoptotic, and/or antioxidant modulatory pathways.

The Antioxidant and Antitumor Efficiency of Litophyton sp. Extract in DMH-Induced Colon Cancer in Male Rats.

One of the most common tumors to cause death worldwide is colon cancer. This study aims to investigate the antitumor potency of Litophyton sp. methanolic extract (LME) against DMH-induced colon cancer in adult male rats. Group (1) normal rats served as the control, group (2) normal rats were ip-injected with LME at a dose of 100 µg/kg/day, group (3) DMH-induced colon cancer animals, and group (4) colon cancer-modeled animals were treated with LME (100 µg/kg/day) for six weeks. The results revealed that injection of LME markedly regenerated the colon cancer pathophysiological disorders; this was monitored from the significant reduction in the values of serum biomarkers (CEA, CA19.9, AFP), cytokines (TNF-α and IL1ß), and biochemical measurements (ALAT, ASAT, urea, creatinine, cholesterol, and triglycerides) matched significant increase of apoptotic biomarkers (CD4+); similarly, colon DNA fragmentation, MDA, and NO levels were down-regulated. In contrast, a remarkable upregulation in colon SOD, GPx, GSH, and CAT levels was noted. Moreover, the colon histopathological architecture showed obvious regenerations. Chromatography of LME resulted in the purification of two polyhydroxylated steroids (1 and 2) with potential cytotoxic activities. LME performed therapeutic potential colon tumorigenesis; therefore, LME may have a promising chemo-preventive feature against colon cancer, probably via enhancement of the apoptosis pathway, improvement of the immune response, reduction of inflammation, or/and restoration of the impaired oxidative stress.

Cardioprotective and Antioxidant Efficiency of Balanites aegyptiaca Extract Against Doxorubicin® Complication.

<b>Background and Objective:</b> The use of Doxorubicin^® (Doxo) in the treatment of different tumours is restricted due to its cardiotoxicity. The objective of this study was to determine the protective effect of<i> Balanites aegyptiaca</i> extract against cardiotoxicity induced by Doxorubicin^® in male rats. <b>Materials and Methods:</b> Adult male rats (140-160) were parted into 6 groups (10 animals each) as follows: Group (1) Normal rats the control, group (2) Rats were administered BAE (200 mg kg¹) orally for 4 weeks, group (3) Rats were treated IP with the anticancer drug (Doxorubicin^®) at the dose of (0.5 mg kg¹) for 4 weeks, group (4) Administrated orally with BAE in combination with Doxo injection for 4 weeks, group (5) Rats orally with BAE before intoxication with Doxo for 4 weeks and finally group (6) Animals post-administration of BAE for 4 weeks after intoxication with Doxo. After 4 weeks of injections. <b>Results:</b> Revealed that BAE succeeded to decline the Doxorubicin cardiotoxicity, this was evidenced by the significant reduction of serum LDH, CK-MB, total cholesterol, triglycerides, HDL, TNF-α, IL-1ß and IL-6 as well as cardiac MDA and nitric oxide levels coupled with marked improvement in serum LDL, PON1 as well as cardiac GSH, SOD and CAT. Moreover, the BAE induced prominent regeneration of the cardiac muscle. <b>Conclusion:</b> <i>Balanites aegyptiaca</i> extract may be a promising cardio-protector against Doxorubicin^® toxicity mediated through their antioxidant and radical scavenging activities.

Nephroprotective Effect of Costus (Saussurea costus) Ethanolic Extract on Oxaliplatin®-induced Nephrotoxicity in Adult Male Wistar Rats.

<b>Background and Objective:</b> Oxaliplatin^® is an antineoplastic platinum-based compound; nephrotoxicity is one of its most serious side effects. This study aimed to explore the nephroprotective potential of Costus Ethanolic Extract (CEE) against Oxaliplatin^®-induced nephrotoxicity. <b>Materials and Methods:</b> Adult male Wistar rats, weighting 140-160 g, were randomly divided into four groups: (1) Normal rats, (2) Rats ingested with CEE (67.08 mg kg¹ day¹), (3) Rats injected (ip) with Oxaliplatin^® (10 mg kg¹ week¹) and (4) rats treated with CEE in combination Oxaliplatin^® injection. <b>Results:</b> After six weeks of treatments, the results revealed that CEE ingestion along with Oxaliplatin^® injection markedly minimized the Oxaliplatin^®-induced renal deterioration; this was evidenced by the significant reduction in serum urea, creatinine, uric acid, Tumor Necrosis Factor Alpha (TNF-α), Interleukin 1Beta (IL¹ß) and Sodium ion (Na⁺) levels as well as kidney Malondialdehyde (MDA), Nitric Oxide (NO) and DNA fragmentation values. Controversially, a marked rise in serum Calcium, Potassium Ion (K⁺) and Cluster of Differentiation 4 (CD4) levels besides renal Glutathione (GSH), Catalase (CAT) and Superoxide Dismutase (SOD) values. Similarly, the histopathological findings confirmed the biochemical ones as the CEE restored the Oxaliplatin^®-induced histological degenerations. <b>Conclusion:</b> In conclusion, CEE exhibited nephron-protection efficiency against Oxaliplatin^®-induced nephrotoxicity; this promising effect may be achieved through the antioxidant and radical scavenging activities of its constituents.

Immunohistochemical differential diagnosis between urothelial carcinoma and prostate adenocarcinoma among Egyptian patients.

The aim of the present study was to differentiate between prostate adenocarcinoma and urothelial carcinoma among Egyptian patients by immunohistochemical methods. Two groups of patients were used: urothelial group, consisted of 9 cystitis, 21 transitional cell carcinoma (TCC) and 5 urinary bladder mucoid adenocarcinoma (MAC) and prostatic group, consisted of 9 nodular prostatic hyperplasia (NPH) and 21 prostatic adenocarcinoma (PAC). H-E stained sections were performed to confirm the diagnosis and evaluate the histopathological characteristics of the tumor. Immunohistochemical techniques were used for detection of P63, CK7, CK10 and PSA. The results showed that in urothelial group, positive p63and CK7 immunostaining was observed in all cases of cystitis, transitional cell carcinoma and urinary bladder mucoid adenocarcinoma. All cases of cystitis, transitional cell carcinoma and urinary bladder mucoid adenocarcinoma were CK10 and PSA negative. In prostate group, positive p63 immunostaining was observed in all cases of NPH and in prostatic adenocarcinoma. Positive CK7 immunostaining was observed in all cases of NPH while all cases of prostatic adenocarcinoma were CK7 negative. Positive CK10 immunostaining was observed in all cases of NPH. In prostatic adenocarcinoma, 11 cases were CK10 positive and 10 cases were CK10 negative. All cases of NPH and prostatic adenocarcinoma were PSA positive. In conclusion, the result of the present work proved that p63 and CK7 can be used along with other markers to differentiate between adenocarcinoma of prostate and urothelial carcinoma of the bladder. Also, CK10 and PSA are useful for distinguishing prostate cancer from urothelial carcinoma.

Metiram-induced nephrotoxicity in albino mice: effect of licorice aqueous extract.

The present study was designed to estimate the effect of aqueous extract of licorice on metiram toxicity in mice. Treating mice with metiram at a dose level of [1/2] LD(50) daily for 3 weeks induced many histological changes in the kidney cortex. The renal tubules lost their characteristic appearance and their lining epithelial cells were degenerated. The glomeruli were atrophied and the renal blood vessels were congested. The intertubular spaces infiltrated by inflammatory leukocytic cells. Metiram caused an increase in proliferating cell nuclear antigen (PCNA) expression in nuclei of tubular epithelial cells. Metiram also caused marked elevation in serum creatinine and blood urea nitrogen. Treating animals with metiram and licorice aqueous extract led to an improvement, in both biochemical and histopathological alterations. These results proved that licorice had an ameliorative effect against kidney injury induced by metiram and this effect may be attributed to its antioxidant activity.