Disease relevance of Citral

• The results presented confirm the previous suggestion that a free radical-peroxide mechanism is involved in citral induced hemolysis [1].
• Early stages of the pathogenesis of rat ventral prostate hyperplasia induced by citral [2].
• When tested against Fusarium oxysporum and F. solani, fungal root pathogens of Citrus, enhanced toxicity by citral in the presence of UV-A was demonstrated, while dark toxicity was negligible [3].
• Typical lesions of benign prostatic hyperplasia (BPH) were induced experimentally in the ventral prostate of adolescent (6 week old) male rats by citral, a nonsteroidal compound [2].
• Those E. coli strains carrying a gene leading to catalase deficiency (katF) are particularly sensitized to inactivation by citral and UV-A treatment when compared to catalase proficient strains (katF+) [3].

Psychiatry related information on Citral

• On postnatal day 11, oligodeoxynucleotides were infused directly into the bilateral olfactory bulbs through cannulae implanted prior to training in a classical conditioning paradigm with citral odor and foot shock [4].

High impact information on Citral

• The formation of these spinules during light adaptation is impaired in the presence of citral, a competitive inhibitor of the dehydrogenase responsible for the generation of retinoic acid in vivo [5].
• The feasibility of this approach was demonstrated by the ability of citral treatment and v-erbA mRNA injection to reduce the teratogenic effects of exogenous retinol and retinoic acid, respectively, in early Xenopus development [6].
• Interestingly, v-erbA mRNA injection and citral treatment of gastrula stage embryos resulted in tadpoles with a similar set of developmental defects [6].
• Although citral had little effect on epidermal ornithine decarboxylase activity when applied alone, it potentiated the induction of ornithine decarboxylase activity by 12-O-tetradecanoylphorbol-13-acetate [7].
• Consistent with this idea, exogenous FGF8 was able to prevent cell death, rescue most of the morphological defects and was able to prevent a decrease in retinoic acid receptorbeta (Rarbeta) expression caused by Citral [8].

Chemical compound and disease context of Citral

• Comparison of the characteristics of the hemolysis induced by high and low citral concentrations, indicated that two mechanisms are involved--a non specific steroid--terpenoid or glutathione depletion mechanism dominating at high citral concentrations and a free radical mechanism dominating at low citral concentrations [9].
• Glucose inhibited citral induced hemolysis and restored the depleted cellular stores of GSH [1].
• The order of toxicity toward P. digitatum was, starting with the most toxic, citral > nerol/geraniol > geranic acid > methylheptenone >> acetaldehyde [10].
• Inclusion of 4-methylpyrazole and citral, enzyme inhibitors for the conversion of retinol to retinoic acid, produced cardiovascular abnormalities in embryos similar to those observed in vitamin A deficiency [11].
• Addition of small amounts of citral or 5,7-dimethoxycoumarin, and linalool to the stored lemon peel extract would bring back the toxicity to the rates of fresh lemons extracts [12].

Biological context of Citral

• The mechanism of Citral effects was a specific increase in programmed cell death on the lateral (lateral nasal prominence) but not the medial side (frontonasal mass) of the nasal pit [8].
• Citral prevented upregulation of Fgf8 along the lateral edge and this may have contributed to the specific increase in programmed cell death in the lateral nasal prominence [8].
• MgCo6Ge6 possesses a remarkable activity and selectivity for the hydrogenation of cis/trans-citral to geraniol and nerol [13].
• Compared to ROH alone, ROH plus citral treatment resulted in three-fold less tRA synthesis and a > 65% attentuation of RA-responsive reporter gene activity which persisted through 72 h [14].
• This hypothetical cascade of RA signaling was supported by our findings that inhibition of the ROL-->RA converting enzyme system by citral abolished the Ca2+-mediated transactivation of the CAT gene in a nontoxic manner [15].

Anatomical context of Citral

• These citral-treated limb buds frequently formed truncated cartilage elements and the defects were rescued by simultaneous treatment with an appropriate concentration of RA [16].
• Thus, citral is not suitable for use in attempts to distinguish between retinoid conversions catalyzed by dehydrogenases in the cytoplasm and by P450 cytochromes in the endoplasmic reticulum [17].
• CFA itself, however, had a proliferative action on the prostatic epithelium, and it augmented the hyperplastic changes induced by citral and even induced atypical transformations of the acinar epithelium [18].
• The concentration of intracellular glutathione diminished in citral treated erythrocytes [1].
• RESULTS: CsA did not induce hyperplastic changes or abolish the ability of citral to promote hyperplastic changes or to affect the extent of the lymphocytic exudate in the stroma [18].

Associations of Citral with other chemical compounds

• Retinol oxidation by epidermal extracts was inhibited by the alcohol dehydrogenase inhibitor 4-methylpyrazole and by the polyene citral [19].
• The structure-activity relationship study revealed that geranial, an E-isomer, was mainly responsible for the inducing activity of citral mixture and the aldehyde group conjugated with a trans-double bond is an essential structural factor [20].
• RA, however, reversed the effect of citral on development and stimulated cell proliferation [21].
• Although most reported cases of citrus peel allergy are due to d-limonene, for our patient, reactions to patch tests for geraniol and citral, two minor components of citrus peel oil, were positive, whereas those for d-limonene were negative [22].
• No change was observed on the expression of CD45 and CD40 after treatment with a mild or a weak contact sensitizer, citral and citronellal respectively [23].

Gene context of Citral

• The MEK inhibitor PD98059 was continuously infused into the OB of postnatal day 11 rat pups during a 30-min training session regarding the pairing of citral odor and foot shock [24].
• The Vmax for citral with the E1 isozyme was higher than those of the E2 and E3 isozymes which explains its fast recovery following inhibition by citral and suggests that E1 may be the enzyme involved in vivo citral metabolism [25].
• We have carried out experiments that have used Citral, a RALDH antagonist, to address the function of retinoid signaling from the nasal pit in a whole embryo model [8].
• In the first experiment, postnatal day 11 rat pups were trained in an olfactory associative learning task with citral odor and foot shock as the conditioned and unconditioned stimuli, respectively [26].
• Evidence of ALDH-mediated citral oxidation was not seen in either subcellular fraction [27].

Analytical, diagnostic and therapeutic context of Citral

• Castration prior to citral administration prevented such BPH changes; however, citral did not prevent the involutive lesions of castration [2].
• A study of the potential effects of microencapsulation on the toxicity of citral was conducted in 14-day continuous feeding studies with both sexes of F344 rats and B6C3F1 mice [28].
• The HPLC method developed in this study showed an excellent performance (linearity, precision, accuracy and specificity) and can be applied to assay citral in volatile oil [29].
• The reference method for both types of oil was the BP monograph titration assay for the citral content of lemon oil and calibrations were constructed using these reference data [30].
• Low doses of citral and geraniol (threshold ca. 10(-4) M) reversibly increased the frequency of spontaneous foregut contractions and abolished them at 2 x 10(-3) M (together with response to electrical stimulation) [31].

References