Protocatechuic acid attenuates lipopolysaccharide-induced septic lung injury in mice: The possible role through suppressing oxidative stress, inflammation and apoptosis.

Here, we investigated the protective efficacy of protocatechuic acid (PCA) against lipopolysaccharide (LPS)-induced septic lung injury. Eighty-two male Balb/c mice were divided into six groups: control, PCA30 (30 mg/kg), LPS (10 mg/kg), PCA10-LPS, PCA20-LPS, and PCA30-LPS treated with 10, 20 and 30 mg/kg PCA, respectively, for seven days before intraperitoneal LPS injection. PCA pre-treatment, especially at higher dose, significantly reduced LPS-induced lung tissue injury as indicated by increased heat shock protein 70 and antioxidant molecules (reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) accompanied by lower oxidative stress indices (malondialdehyde and nitric oxide). PCA administration decreased inflammatory mediators including myeloperoxidase, nuclear factor kappa B (NF-κB p65), and pro-inflammatory cytokines, and prevented the development of apoptotic events in the lung tissue. At the molecular level, PCA downregulated mRNA expression of nitric oxide synthase 2, C/EBP homologous protein, and high mobility group box1 in the lungs of all PCA-LPS treated mice. Thus, PCA-pre-treatment effectively counteracted sepsis-induced acute lung injury in vivo by promoting and antioxidant status, while inhibiting inflammation and apoptosis. PRACTICAL IMPLICATIONS: Sepsis-mediated organ dysfunction and high mortality is aggravated by acute lung injury (ALI). Therefore, new therapeutic approaches are needed to encounter sepsis-mediated ALI. Protocatechuic acid (PCA) is a naturally occurring phenolic acid with various biological and pharmacological activities. PCA is abundant in edible plants including Allium cepa L., Oryza sativa L., Hibiscus sabdariffa, Prunus domestica L., and Eucommia ulmoides. In this investigation we studied the potential protective role of pure PCA (10, 20 and 30 mg/kg) on LPS-mediated septic lung injury in mice through examining oxidative challenge, inflammatory response, apoptotic events and histopathological changes in addition to evaluating the levels and mRNA expression of heat shock protein 70, C/EBP homologous protein and high mobility group box1 in the lung tissue. The recorded results showed that PCA pre-administration was able to significantly abrogate the damages in the lung tissue associated septic response. This protective effect comes from its strong antioxidant, anti-inflammatory, and anti-apoptotic activities, suggesting that PCA may be applied to alleviate ALI associated with the development of sepsis.

Impact of Coenzyme Q10 Administration on Lead Acetate-Induced Testicular Damage in Rats.

Exposure to lead (Pb) causes multiorgan dysfunction including reproductive impairments. Here, we examined the protective effects of coenzyme Q10 (CoQ10) administration on testicular injury induced by lead acetate (PbAc) exposure in rats. This study employed four experimental groups (n = 7) that underwent seven days of treatment as follows: control group intraperitoneally (i.p.) treated with 0.1 ml of 0.9% NaCl containing 1% Tween 80 (v : v), CoQ10 group that was i.p. injected with 10 mg/kg CoQ10, PbAc group that was i.p. treated with PbAc (20 mg/kg), and PbAc+CoQ10 group that was i.p. injected with CoQ10 2 h after PbAc. PbAc injection resulted in increasing residual Pb levels in the testis and reducing testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Additionally, PbAc exposure resulted in significant oxidative damage to the tissues on the testes. PbAc raised the levels of prooxidants (malondialdehyde and nitric oxide) and reduced the amount of endogenous antioxidative proteins (glutathione and its derivative enzymes, catalase, and superoxide dismutase) available in the cell. Moreover, PbAc induced the inflammatory response as evidenced by the upregulation of inflammatory mediators (tumor necrosis factor-alpha and interleukin-1 beta). Further, PbAc treatment induced apoptosis in the testicular cells, as indicated by an increase in Bax and caspase 3 expression, and reduced Bcl2 expression. CoQ10 supplementation improved testicular function by inhibiting Pb accumulation, oxidative stress, inflammation, cell death, and histopathological changes following PbAc exposure. Our findings suggest that CoQ10 can act as a natural therapeutic agent to protect against the reproductive impairments associated with PbAc exposure.

Neuromodulatory effects of green coffee bean extract against brain damage in male albino rats with experimentally induced diabetes.

Diabetes mellitus is an increasing metabolic disease worldwide associated with central nervous system disorders. Coffee is a widely consumed beverage that enriched with antioxidants with numerous medicinal applications. Accordingly, the present study aimed to investigate the therapeutic potential of orally administered green coffee bean water extract (GCBWE) against cortical damage induced by high fat diet (HFD) followed by a single injection of streptozotocin (STZ) in rats. Metformin (Met) was used as standard antidiabetic drug. Animals were allocated into six groups: control, GCBWE (100 mg/kg), HFD/STZ (40 mg/kg), HFD/STZ + GCBWE (50 mg/kg), HFD/STZ + GCBWE (100 mg/kg) and HFD/STZ + Met (200 mg/kg) which were treated daily for 28 days. Compared to control rats, HFD/STZ-treated rats showed decreased levels of cortical dopamine, norepinephrine and serotonin with marked increases in their metabolites. Further, HFD/STZ treatment resulted in notable elevations in malondialdehyde, protein carbonyl and total nitrite levels paralleled with declines in antioxidant markers (SOD, CAT, GPx, GR and GSH) and down-regulations of Sod2, Cat, GPx1 and Gsr gene expression. Neuroinflammation was evident in diabetic animals by marked elevations in TNF-α, IL-1ß and up-regulation of inducible nitric oxide synthase. Significant rises incaspase-3 and Bax with decline in Bcl-2 level were noticed in diabetic rats together with similar results in their gene expressions. Cortical histopathological examination supported the biochemical and molecular findings. GCBWE administration achieved noteworthy neuroprotection in diabetic animals in most assessed parameters. The overall results suggested that antioxidant, anti-inflammatory; anti-apoptotic activities of GCBWE restored the cortical neurochemistry in diabetic rats.

Identification of microRNA signature and potential pathway targets in prostate cancer.

Prostate cancer (PC) is the most common and the second leading cause of cancer-related death among American men. Early diagnosis is a prerequisite to improving therapeutic benefits. However, the current clinical biomarkers for PC do not reliably decipher indolent PC from other urogenital disorders. Thus, effective clinical intervention necessitates development of new biomarkers for early detection of PC. The present study aimed to identify the miRNA signature in organ-confined (Gleason Score 6) prostate tumors. MicroRNA (miRNA/miR) array analysis identified 118 upregulated and 73 downregulated miRNAs in microdissected tumors in comparison to matched neighboring normal prostate epithelium. The miRs-Plus-A1083, -92b-5p, -18a-3p, -19a-3p, -639, -3622b-3p, -3189-3p, -155-3p, -410, -1179, 548b-5p, and -4469 are predominantly expressed (7-11-fold), whereas miRs-595, 4490, -3120-5p, -1299, -21-5p, -3677-3, -let-7b-5p, -5189, 3-121-5p, -4518, -200a-5p, -3682-5p, -3689d, -3149 represent the most downregulated (12-113-fold) miRNAs in microdissected prostate tumors. The array expression profile of selected miRNA signature and their potential mRNA targets was validated by qRT-PCR analysis in PC cell lines. Integrated in silico and computational prediction analyses demonstrated that the dysregulated miRNA signature map to key regulatory factors involved in tumorigenesis, including cell cycle, apoptosis, and p53 pathways. The newly identified miRNA signature has potential clinical utility as biomarkers, prognostic indicators, and therapeutic targets for early detection of PC. Further studies are needed to assess the functional significance and clinical usefulness of the identified miRNAs. Impact Statement To our knowledge his is the first study of identifying miRNA signatures in microdissected indolent (Gleason score 6) prostate cancer in comparison to matched normal prostate epithelium. By employing in silico and computational prediction analysis, the study provides a landscape of potential miRNA targets and key cellular pathways involved in prostate tumorigenesis. Identification if miRNAs and their relevant targets and pathways pave the way for underpinning their mechanistic role of miRNAs in human prostate tumorigenesis, and possibly other human cancers. Importantly, the outcome of the study has important clinical implications for the management of prostate cancer, including the use of miRNA(s) as biomarkers for early detection of prostate cancer.