Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease

Expert Opinion on Drug Metabolism and Toxicology

Volumn 12, Issue 10, 2016, Pages 1181-1196

  Bizzarri, Mariano ^a   Fuso, Andrea ^a,b   Dinicola, Simona ^a   Cucina, Alessandra ^a,c   Bevilacqua, Arturo ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b IRCCS FONDAZIONE SANTA LUCIA   (Italy)

^c POLICLINICO UMBERTO I   (Italy)

Author keywords

cell signalling; inositol phosphates; inositolphosphoglycans; Myo inositol; phosphoinositides

Indexed keywords

ANTINEOPLASTIC AGENT; GLYCAN; GLYCOSYLPHOSPHATIDYLINOSITOL DERIVATIVE; INOSITOL; INOSITOL DERIVATIVE; INOSITOL PHOSPHATE; ION CHANNEL; MESSENGER RNA; PHOSPHATIDYLINOSITIDE; PHOSPHOGLYCAN; PHOSPHOLIPID; UNCLASSIFIED DRUG; PHOSPHATIDYLINOSITOL;

ALZHEIMER DISEASE; BIOSYNTHESIS; CANCER CHEMOTHERAPY; CATABOLISM; CHRONIC DISEASE; CONGENITAL MALFORMATION; CYTOSKELETON; DEVELOPMENTAL DISORDER; DIARRHEA; DIET; DIZZINESS; DRUG BIOAVAILABILITY; DRUG EXCRETION; DRUG METABOLISM; DRUG SAFETY; DRUG TRANSPORT; EMBRYO; GYNECOLOGIC DISEASE; HEADACHE; HEALTH; HUMAN; INSOMNIA; ISOMER; LUNG FUNCTION; MANIA; METABOLIC SYNDROME X; NAUSEA; NEOPLASM; NEUROLOGIC DISEASE; NONHUMAN; OOCYTE; PHARMACODYNAMICS; RESPIRATORY DISTRESS SYNDROME; REVIEW; SOMNOLENCE; SPERM; ANIMAL; BIOAVAILABILITY; GENOMICS; METABOLISM; METABOLOMICS; PHYSIOLOGY; PROCEDURES; SIGNAL TRANSDUCTION;

ANIMALS; BIOLOGICAL AVAILABILITY; GENOMICS; HUMANS; INOSITOL; INOSITOL PHOSPHATES; METABOLOMICS; PHOSPHATIDYLINOSITOLS; SIGNAL TRANSDUCTION;

EID: 84987849554     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1080/17425255.2016.1206887     Document Type: Review

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123. A.M.Gustafson, R.Soldi, C.Anderlind, et al. Airway PI3K pathway activation is an early and reversible event in lung cancer development. Sci Transl Med. 2010;2(26):26ra25.
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125. A.K.M.Shamsuddin, I.Vucenik. IP6 & inositol in cancer prevention and therapy. Curr Cancer Ther Rev. 2005;1(3):259–269.
126. L.W.Wattenberg, R.D.Estensen. Chemopreventive effects of myo-inositol and dexamethasone on benzo(a)pyrene and 4-(methyl-nitrosamine)-1-(3-pyridyl)-1-butanone-induced pulmonary carcinogenesis in female A/J mice. Cancer Res. 1996;56(22):5132–5135.
127. S.S.Hecht, P.Upadhyaya, M.Wang, et al. Inhibition of lung tumorigenesis in A/J mice by N-acetyl-S-(N-2-phenethylthiocarbamoyl)-L-cysteine and myo-inositol, individually and in combination. Carcinogenesis. 2002;23(9):1455–1461.
128. S.Lam, A.McWilliams, J.LeRiche, et al. A phase I study of myo-inositol for lung cancer chemoprevention. Cancer Epidemiol Biomarkers Prev. 2006;15(8):1526–1531.
129. N.H.Shafie, N.Mohd Esa, H.Ithnin, et al. Preventive Inositol Hexaphosphate extracted from rice bran inhibits colorectal cancer through involvement of Wnt/β-catenin and COX-2 pathways. Biomed Res Int. 2013;2013:681027.
130. S.Windhorst, H.Lin, C.Blechner, et al. Tumour cells can employ extracellular Ins(1,2,3,4,5,6)P6 and multiple inositol-polyphosphate phosphatase 1 (MINPP1) dephosphorylation to improve their proliferation. Biochem J. 2013;450(1):115–125.
131. M.Gu, K.Raina, C.Agarwal, et al. Inositol hexaphosphate downregulates both constitutive and ligand-induced mitogenic and cell survival signaling, and causes caspase-mediated apoptotic death of human prostate carcinoma PC-3 cells. Mol Carcinog. 2010;49(1):1–12.• This is the first paper suggesting that the reduced myo/d-chiro-Ins ratio may play a pathogenetic role in PCOS patients.
132. S.Djiogue, A.H.Nwabo Kamdje, L.Vecchio, et al. Insulin resistance and cancer:the role of insulin and IGFs. Endocr Relat Cancer. 2013;20(1):R1–R17.
133. A.Izzotti, R.Balansky, F.D’Agostini, et al. Relationships between pulmonary micro-RNA and proteome profiles, systemic cytogenetic damage and lung tumors in cigarette smoke-exposed mice treated with chemopreventive agents. Carcinogenesis. 2013;34(10):2322–2329.
134. F.Kassie, S.Kalscheuer, I.Matise, et al. Inhibition of vinyl carbamate-induced pulmonary adenocarcinoma by indole-3-carbinol and myo-inositol in A/J mice. Carcinogenesis. 2010;31(2):239–245.
135. F.Kassie, T.Melkamu, A.Endalew, et al. Inhibition of lung carcinogenesis and critical cancer-related signaling pathways by N-acetyl-S-(N-2-phenethylthiocarbamoyl)-l-cysteine, indole-3-carbinol and myo-inositol, alone and in combination. Carcinogenesis. 2010;31(9):1634–1641.• The paper provides data upon the involvement of inositol in sperm functionality.
136. W.Han, J.J.Gills, R.M.Memmott, et al. The chemopreventive agent myoinositol inhibits Akt and extracellular signal-regulated kinase in bronchial lesions from heavy smokers. Cancer Prev Res (Phila). 2009;2(4):370–376.
137. A.M.GustafsonI, R.Soldi, C.Anderlind, et al. Airway PI3K pathway activation is an early and reversible event in lung cancer development. Sci Transl Med. 2010;2(26):26ra25.
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139. S.Dinicola, G.Fabrizi, M.G.Masiello, et al. Inositol induces mesenchymal-epithelial reversion in breast cancer cells through cytoskeleton rearrangement. Exp Cell Res. 2016;345(1):37–50.
140. T.Koguchi, C.Tanikawa, J.Mori, et al. Regulation of myo-inositol biosynthesis by p53-ISYNA1 pathway. Int J Oncol. 2016;48(6):2415–2424.
141. V.Guarner, C.Tordet, J.R.Bourbon. Effects of maternal protein-calorie malnutrition on the phospholipid composition of surfactant isolated from the fetal and neonatal rat lungs. Compensation by inositol and lipid supplementation. Pediatr Res. 1992;31(6):629–635.
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143. A.P.Gilmore, K.Burridge. Regulation of vinculin binding to talin and actin by phosphatidyl-inositol-4-5-bisphosphate. Nature. 1996;381(6582):531–535.
144. G.R.Pereira, L.Baker, J.Egler, et al. Serum myoinositol concentrations in premature infants fed human milk, formula for infants, and parenteral nutrition. Am J Clin Nutr. 1990;51(4):589–593.• A clear relationship between embryo quality and inositol supplementation is discussed in this study.
145. S.Dinicola, T.T.Chiu, V.Unfer, et al. The rationale of the myo-inositol and D-chiro-inositol combined treatment for polycystic ovary syndrome. J Clin Pharmacol. 2014;54(10):1079–1092.
146. A.Bevilacqua, M.Bizzarri. Physiological role and clinical utility of inositols in polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2016. pii:S1521-6934(16)30006-2. [Epub ahead of print]
147. Z.Kamenov, G.Kolarov, A.Gateva, et al. Ovulation induction with myo-inositol alone and in combination with clomiphene citrate in polycystic ovarian syndrome patients with insulin resistance. Gynecol Endocrinol. 2015;31(2):131–135.
148. A.Hautanen. Synthesis and regulation of sex hormone-binding globulin in obesity. Int J Obes Relat Metab Disord. 2000;24(Suppl 2):S64–70.
149. M.Bizzarri, A.Cucina, S.Dinicola, et al. Does myo-inositol effect on PCOS follicles involve cytoskeleton regulation? Med Hypotheses. 2016;91:1–5.
150. M.Rondanelli, S.Perna, M.Faliva, et al. Focus on metabolic and nutritional correlates of polycystic ovary syndrome and update on nutritional management of these critical phenomena. Arch Gynecol Obstet. 2014;290(6):1079–1092.•• A relevant paper reporting the involvement of inositol in modulating a specific set of genes during bone developmental processes.
151. T.H.Sun, D.B.Heimark, T.Nguygen, et al. Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared to Wistar controls. Biochem Biophys Res Commun. 2002;293(3):1092–1098.
152. R.Isabella, E.Raffone. Does ovary need D-chiro-inositol? J Ovarian Res. 2012;5(1):14.
153. J.E.Nestler, V.Unfer. Reflections on inositol(s) for PCOS therapy:steps toward success. Gynecol Endocrinol. 2015;31(7):501–505.
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155. K.M.Lowther, V.N.Weitzman, D.Maier, et al. Maturation, fertilization, and the structure and function of the endoplasmic reticulum in cryopreserved mouse oocytes. Biol Reprod. 2009;81(1):147–154.
156. T.T.Chiu, M.S.Rogers, C.Briton-Jones, et al. Effects of myo- inositol on the in-vitro maturation and subsequent development of mouse oocytes. Hum Reprod. 2003;18(2):408–416.
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158. A.S.Goldman, M.P.Goto. Biochemical basis of the diabetic embryopathy. Isr J Med Sci. 1991;27(8–9):469–477.
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162. O.Voevodskaya, P.C.Sundgren, O.Strandberg, et al. Myo-inositol changes precede amyloid pathology and relate to APOE genotype in Alzheimer disease. Neurology. 2016;86(19):1754–1761.•• The paper summarizes data upon the inhibitory effect of Myo- and scyllo-inositol on β-amyloid proteins and on γ-secretase activity.
163. E.Ito, K.Oka, R.Etcheberrigaray, et al. Internal Ca2+ mobilization is altered in fibroblasts from patients with Alzheimer disease. Proc Natl Acad Sci U S A. 1994;91(2):534–538.
164. F.M.LaFerla. Calcium dyshomeostasis and intracellular signalling in Alzheimer’s disease. Nat Rev Neurosci. 2002;3(11):862–872.
165. M.A.Leissring, M.P.Murphy, T.R.Mead, et al. A physiologic signaling role for the gamma -secretase-derived intracellular fragment of APP. Proc Natl Acad Sci U S A. 2002;99(7):4697–4702.• The first study evidencing the wide range effects on gene expression pattern downstream of myo-inositol addiction or removal.
166. K.H.Cheung, D.Shineman, M.Müller, et al. Mechanism of Ca2+ disruption in Alzheimer’s disease by presenilin regulation of InsP3 receptor channel gating. Neuron. 2008;58(6):871–883.• The first systems-biology approach in investigating how perturbation of the inositol network may influence key biological pathways in cancer.
167. S.A.Jesch, X.Zhao, M.T.Wells, et al. Genome-wide analysis reveals inositol, not choline, as the major effector of Ino2p-Ino4p and unfolded protein response target gene expression in yeast. J Biol Chem. 2005;280(10):9106–9118.
168. B.L.Puniya, L.Allen, C.Hochfelder, et al. Systems perturbation analysis of a large-scale signal transduction model reveals potentially influential candidates for cancer therapeutics. Front Bioeng Biotechnol. 2016;4:10. doi:10.3389/fbioe.2016.00010.
169. Y.Shi, A.N.Azab, M.N.Thompson, et al. Inositol phosphates and phosphoinositides in health and disease. Subcell Biochem. 2006;39:265–292.
170. M.R.Macbeth, H.L.Schubert, A.P.Vandemark, et al. Inositol hexakisphosphate is bound in the ADAR2 core and required for RNA editing. Science. 2005;309(5740):1534–1539.•• The paper demonstrated that IP2 may significantly modulate actin synthesis, providing the first demonstration of a link between myo-inositol and cytoskeleton dynamics.
171. T.Suzuki, H.Hara. Phytatehydrolysate induces circumferential F-actin ring formation at cell–cell contacts by a Rho-associated kinase dependent mechanism in colorectal cancer HT-29 cells. Mol Nutr Food Res. 2010;54(12):1807–1818.
172. A.M.Seeds, J.D.York. Inositol polyphosphate kinases:regulators of nuclear function. Biochem Soc Symp. 2007;74(74):183–197.• A comprehensive survey of the recent studies investigating functions of the nuclear inositol network.
173. A.R.Odom, A.Stahlberg, S.R.Wente, et al. A role for nuclear inositol 1,4,5-trisphosphate kinase in transcriptional control. Science. 2000;287(5460):2026–2029.
174. X.Shen, H.Xiao, R.Ranallo, et al. Modulation of ATP-dependent chromatin-remodeling complexes by inositol polyphosphates. Science. 2003;299(5603):112–114.•• A seminal paper highlighting how inositol polyphosphates participate in chromatin remodeling and gene transcription.
175. P.Meinke, A.A.Makarov, P.LêThành, et al. Nucleoskeleton dynamics and functions in health and disease. Cell Health Cytoskelet. 2015;7:55–69.